Predicted and Measured Virucidal Efficacies of Microbicides for Emerging and Re-emerging Viruses Associated with WHO Priority Diseases

Abstract

The World Health Organization has updated its list of priority diseases for 2021 to currently include the following: Ebola virus disease and Marburg virus disease (Filoviridae), Nipah and henipaviral diseases (Paramyxoviridae), Lassa fever (Arenaviridae), Rift Valley fever and Crimean-Congo hemorrhagic fever (Bunyaviridae), Zika (Flaviviridae), COVID-19 (SARS-CoV-2) including Delta, Omicron, and other variants of concern, Middle East respiratory syndrome, severe acute respiratory syndrome (Coronaviridae), and the always present “disease X,” which is a term used for the next emerging pathogen of concern that is not known about today. In this chapter, we review the virucidal efficacy data for microbicides (disinfectants and antiseptics, also known as surface and hand hygiene agents or collectively hygiene agents) for the viruses associated with these diseases. As these diseases are each caused by lipid-enveloped viruses, the susceptibilities of the viruses to virucidal agents are informed by the known hierarchy of susceptibility of pathogens to microbicides. The unique susceptibility of lipid-enveloped viruses to most classes of microbicides is based on the common mechanism of action of envelope-disrupting microbicides. Empirical data supporting this principle and the mitigational role of targeted hygiene in infection prevention and control (IPAC) discussed are presented.

1. Introduction

The World Health Organization (WHO) compiles, each year, a list of priority diseases. As stated in the associated WHO web page [1], the list is intended to encourage “research and development in emergency contexts.” In other words, recognizing that the number of pathogens is very large, the WHO attempts through the Priority List to focus research attention on those diseases posing the greatest risk to public health. In addition, the Priority List serves to promote the development of infection prevention and control (IPAC) “countermeasures” for diseases where such countermeasures are limited or non-existent [1].

In this chapter, we thought it would be of interest to examine the 2021 WHO Priority List (Box 1) to see where the public health community stands with respect to IPAC countermeasures for the listed viruses (see section below). The approach that we have taken involved searching the literature for articles pertaining to virucidal efficacies for microbicides evaluated specifically against the listed viruses. In some cases literature for a specific listed virus was not able to be identified, but literature on listed viruses of the same family were available. The mechanisms of action of microbicides for viruses should apply similarly to different members of a given virus family, although intrafamily exceptions do exist [2, 3].

Box 1.

WHO priority disease list.

The WHO priority diseases [1] are updated periodically in “a list of disease and pathogens [that is] prioritized for R&D in public health emergency contexts.” This tool specifies “which diseases pose the greatest public health risk due to their epidemic potential and/or whether there is no or insufficient countermeasures.”

At present, the priority diseases are:

• COVID-19 [SARS-CoV-2, including its variants]

• Crimean-Congo haemorrhagic fever

• Ebola virus disease and Marburg virus disease

• Lassa fever

• Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS)

• Nipah and henipaviral diseases

• Rift Valley fever

• Zika

• “Disease X”^*

^*Disease X represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease [1].

It should be noted, as a starting point, that even in the absence of empirical data supporting the virucidal efficacy of microbicides for a given emerging or re-emerging virus or mutational variant of a known virus such as emerging variants of SARS-CoV-2, disinfection options still are available for IPAC. For instance, the United States Environmental Protection Agency (U.S. EPA) has invoked an Emerging Viral Pathogen Guidance for Antimicrobial Pesticides [4, 5] specifically to deal with just such a possibility. As stated in the associated U.S. EPA web page, the guidance provides a “process that can be used to identify effective disinfectant products for use against emerging viral pathogens and to permit registrants to make limited claims of their product’s efficacy against such pathogens.” The actual guidance (Guidance to Registrants: Process for Making Claims against Emerging Viral Pathogens not on EPA-registered Disinfectant Labels) [5] outlines “a voluntary two stage process, involving product label amendments and modified terms of registration and applies only to emerging viruses” [4].

The underlying principle driving the U.S. EPA Guidance for Antimicrobial Pesticides is that of the hierarchy of susceptibility of pathogens to microbicides (the so-called Spaulding Classification [6]). In the U.S. EPA guidance [5], viruses are classified into three categories, ranked from lesser to greater susceptibility to microbicides: small, non-enveloped viruses; large, non-enveloped viruses; and enveloped viruses. A revised hierarchy of susceptibility of pathogens to microbicides [7, 8, 9, 10] spans the range of susceptibilities from most susceptible (enveloped viruses) to least susceptible (prions). This known hierarchy of susceptibility of pathogens to microbicides gives the public health community a starting point for IPAC countermeasures to be used for emerging pathogens, per the U.S. EPA [4].

2. The current WHO Priority List

The current WHO Priority disease list (Box 1) consists of viral diseases and Disease X, the latter being a placeholder that is always included in these lists. Disease X is used for the next unknown pathogen with the potential to cause a serious international epidemic. The viral families represented include Arenaviridae (Lassa fever virus); Bunyaviridae (Crimean-Congo hemorrhagic fever virus and Rift Valley fever virus); Coronaviridae (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] causing COVID-19, Middle East respiratory syndrome coronavirus [MERS-CoV], and severe acute respiratory syndrome coronavirus [SARS-CoV]); Filoviridae (Ebola virus and Marburg virus]; Flaviviridae (Zika virus); and Paramyxoviridae (Nipah virus and henipaviruses).

Some of the characteristics of these viruses and their differences and commonalities are displayed in Table 1. Interestingly, these are each relatively large, lipid-enveloped viruses having single-stranded RNA genomes. Primary host infection of hemorrhagic viruses can be through insect vectors (arboviruses and flaviviruses), eating contaminated meat (filoviruses), consuming products in contact with bodily fluids of bats or pigs, such as blood, urine, nasal, respiratory droplets, and saliva (Nipah or henipaviruses), or exposure to contaminated rodent urine (Lassa virus). Once a human host is infected, the virus may be transmitted through contaminated bodily fluids and/or respiratory droplets. Non-hemorrhagic viruses such as SARS-CoV, SARS-CoV-2, and MERS-CoV are believed to be spread primarily by respiratory aerosols/droplets, although fomite transmission is also believed to play a role [10]. Case mortality rates vary, with SARS-CoV-2 having perhaps the lowest (2.1%), and Ebola Zaire virus among the highest (∼90%). These viruses retain infectivity for hours to days after being deposited experimentally on non-porous surfaces [10].

Virus	Family	Particle size	Lipid envelope	Genomea (segments)	Reservoir species	Reference(s)
Lassa virus	Arenaviridae	50–300 nm	Yes	±ssRNA(2)	Rodent	[11]
RVFV	Bunyaviridae	90–100 nm	Yes	−ssRNA(3)	Mosquito	[11]
CCHFV	Bunyaviridae	90–100 nm	Yes	−ssRNA(3)	Tick	[11]
MERS-CoV	Coronaviridae	90–130 nm	Yes	+ssRNA(1)	Bat	[12]
SARS-CoV	Coronaviridae	90–130 nm	Yes	+ssRNA(1)	Bat	[12]
SARS-CoV-2	Coronaviridae	90–130 nm	Yes	+ssRNA(1)	Batb	[12]
Ebola virus	Filoviridae	80 × 14,000 nm	Yes	−ssRNA(1)	Bat	[11]
Marburg virus	Filoviridae	80 × 14,000 nm	Yes	−ssRNA(1)	Bat	[11]
Zika virus	Flaviviridae	50 nm	Yes	+ssRNA	Mosquito	[11]
Nipah virus	Paramyxoviridae	40–1900 nm	Yes	−ssRNA(1)	Bat	[13]

Table 1.

Characteristics of World Health Organization Priority List viruses.

^a

CCHFV, Crimean-Congo hemorrhagic fever virus; MERS-CoV, Middle East respiratory syndrome coronavirus; RVFV, Rift Valley fever virus; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ±, ambisense; −, negative sense; +, positive sense; ss, single-stranded; segments (1) equates to a non-segmented genome.

^b

Suspected primary host [14].

The relatively high lethality of these viral diseases and the ability of the viruses to survive on surfaces [10] inform the need for effective hygiene interventions for interrupting the cycle of infection. Since these viruses have been placed on the WHO Priority List, one might assume that not much is known about virucidal efficacy of microbicides intended for surface hygiene, hand hygiene, and for rendering contaminated test samples safe for use in diagnostic testing for these viruses. In the remainder of this chapter, we review the information that is available on this topic, in order to address this assumption for the reader. The literature on SARS-CoV-2 virucidal efficacy is being updated continually, so the information presented in this chapter on SARS-CoV-2, specifically, should be considered a snapshot taken at the present point in time (i.e., September 2021).

3. Predicted virucidal efficacy data for microbicides, including surface and hand hygiene agents, against the WHO Priority List viruses

The hierarchy of pathogen susceptibility to microbicides [5, 6, 7, 8, 9, 10] (Figure 1) suggests that certain classes of microbicidal agents should display virucidal efficacy against lipid-enveloped viruses in general. For example, lipid-disrupting agents, such as alcohols, quaternary ammonium compounds (e.g., benzalkonium chloride), phenolics (e.g., para-chloro-meta-xylenol or PCMX), detergents (e.g., soap and Triton X-100), and organic acids (e.g., citric, lactic, and salicylic acids) would be expected to display similar virucidal efficacy for the WHO Priority List viruses, which are exclusively lipid-enveloped viruses. The same is true for protein-denaturing agents (alcohols, phenolics, oxidizers, and organic acids), and genome-degrading agents, such as alcohols and oxidizing agents. Of course, microbicides with virucidal efficacy against less susceptible pathogens, including mycobacteria, large and small non-enveloped viruses, and bacterial spores/protozoan oocysts, and prions, would certainly be expected to display virucidal efficacy against each of these WHO Priority List viruses. Having made these predictions, what do the empirical testing data tell us?

Figure 1.

Hierarchy of susceptibility of pathogens to microbicidal active ingredients. Certain formulated microbicides may include combinations of active ingredients, resulting in synergistic virucidal efficacy greater than that displayed by the individual active ingredients ([15] modified from Sattar [8]).

4. Empirical virucidal efficacy data for microbicides, including surface and hand hygiene agents, against the WHO Priority List viruses

In this section, we review the literature with regard to inactivation of WHO Priority List viruses by microbicides intended for decontamination of surfaces, for hand hygiene, for decontamination of liquids, and for test sample disinfection. Our discussion is limited to chemical microbicides, and specifically to the efficacy of these microbicides against the viruses mentioned in the WHO Priority List. The stated purpose of this review was to identify knowledge gaps for virucidal efficacy against the WHO Priority List viruses. As such, information pertaining to surrogate viruses from other families, or even unlisted viruses from the same families, is considered out of scope for this chapter. In addition, physical inactivation approaches (e.g., heating, ultraviolet radiation, and gamma irradiation), are not in scope for this chapter. A review of physical inactivation approaches for SARS-CoV-2 and other coronaviruses can be found in this book [16].

Inactivation studies evaluate pathogens dried onto a surface or within a suspension, but also may investigate efficacy for inactivating pathogens suspended in the air. Studies evaluating decontamination of surfaces involve the application of viruses, in the absence or presence of a soil load, onto carriers representing different prototypic environmental surfaces of interest (e.g., glass, stainless steel, plastic, etc.). Following drying of the applied virus onto the carrier for a set time period, a small quantity of the microbicide is added and left on for the specified contact (dwell) time. Residual virus is collected using an appropriate medium, and the titer post-treatment is compared to the initial untreated virus titer, with log₁₀ reduction results accounting for any cytotoxicity of the test microbicide or neutralizing reagents used on the host cells used in the respective viral assays.

For suspension inactivation studies, depending on the test methodology chosen, virus is added to a liquid matrix, again in the absence or presence of a soil load. The microbicide is added at the evaluated test concentration and the solution is incubated at the appropriate temperature for the planned contact times. Again, the virus titers post-treatment are compared to the titer applied, with log₁₀ reduction results accounting for any cytotoxicity of the test microbicide or neutralizing reagents used on the host cells used in the respective viral assays. Hand hygiene agents may be tested using suspension methodologies, or using specialized methods designed to recover virus directly from the skin. The hand hygiene agents are tested in vitro, or in vivo mimicking simulated-use (using ex vivo model), or under actual use-conditions in human volunteers. Efficacies of virucidal products intended for administration orally or nasally, and other types of therapeutic virucides, are not addressed in this review.

Because of the differences in testing methodologies used for evaluation of surface disinfection vs. decontamination of liquids or test samples, extrapolations of efficacy from one application to another should be made with caution. Differences in virucidal efficacy testing of microbicides (hand and surface hygiene agents) in liquid vs. on surfaces (inanimate or animate) have been identified, but these differences are typically relative, and may depend on the challenge virus and the microbicide being tested [17].

The virucidal efficacy literature for microbicides against Lassa virus is summarized in Table 2, and that for the bunyaviruses (Crimean-Congo hemorrhagic fever virus and Rift Valley fever virus) is summarized in Table 3. Information on virucidal efficacy for the coronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) is presented in Table 4, and virucidal efficacy for filoviruses (Ebola virus and Marburg virus) is shown in Table 5. Table 6 presents virucidal efficacy data for the flavivirus (Zika virus), and the limited information on virucidal efficacy of microbicides against paramyxoviruses (Nipah virus and other henipaviruses) is summarized in Table 7.

Virus/strain	Active ingredient	Product type	Contact time (min)a	Concentration in test	Efficacy (log10)^b	Reference(s)
Surface hygiene
No literature found
Hand hygiene
No literature found
Suspension inactivation
No literature found
Sample disinfection procedures
Lassa Josiah	Acetic acid	Sample inactivant	15	3% (pH 2.5)	≥3	[18]
Lassa	Phenol/guanidine thiocyanate	Nucleic acid extractant	10	80% of neat	≥4.8	[19]
Lassa	β-Propiolactone	Sample inactivant	30 @ 37°C	0.2%	≥7	[20]
Lassa Josiah	Formalin	Cell fixative	20 days	Neat	Complete (cells)	[21]

Table 2.

Efficacy of microbicides for inactivating the arenavirus Lassa virus.

^a

Contact times at room temperature unless otherwise indicated.

^b

Inactivation matrix was virus stock (virus in culture medium), unless otherwise indicated.

Virus/strain^a	Active ingredient	Product type	Contact time (min)	Concentration in test	Efficacy (log10)^b	Reference(s)
Surface hygiene
No literature found
Hand hygiene
No literature found
Suspension inactivation
RVFV Menya/Sheep/258	β-Propiolactone	Vaccine inactivant	240	3.5 mM	≥7	[22]
	Formalin	Vaccine inactivant	360	0.2%	>6	[22]
	Formalin	Vaccine inactivant				[23]
	Binary ethyleneamine	Vaccine inactivant				[23]
Sample disinfection procedures
RVFV	Phenol/guanidine thiocyanate	Nucleic acid extractant	10	80% of neat	≥6.8	[19]
RVFV	Formaldehyde	Cell fixative	1080	0.4%	≥7.0 (cells)	[24]
RVFV MP12	Formalin	Cell fixative	210 @ 4°C	Neat	Complete (cells)	[21]
CCHFV	FA Lysis Buffer	Sample inactivant	4	Undiluted	>4	[25]

Table 3.

Efficacy of microbicides for inactivating the bunyaviruses Rift Valley fever virus and Crimean-Congo hemorrhagic fever virus.

^a

CCHFV, Crimean-Congo hemorrhagic fever virus; RVFV, Rift Valley fever virus.

^b

Inactivation matrix was virus stock (virus in culture medium), unless otherwise indicated.

Virus^a	Active ingredient	Product type	Contact time (min)	Concentration in test	Efficacy (log10)	Reference(s)
Surface hygiene (glass or steel carriers)
SARS-CoV-2	Ethanol, QAC (DBAS)	Disinfectant spray	1.75	50%, 0.08%	≥4.5	[15]
	QAC (DBAC)	Cleaner	2	0.09%	≥4.0	[15]
	QAC (DBAC)	Pre-impregnated wipes	1.75	0.19%	≥3.5	[15]
	Citric acid	Pre-impregnated wipes	0.5	2.4%	≥3.0	[15]
	Ethanol	Alcohol	1	70%	≥4.7	[26]
	Ethanol	Alcohol	1	70%	∼5	[27]
	2-Propanol	Alcohol	1	70%	≥4.7	[26]
	2-Propanol	Alcohol	1	70%	∼5	[27]
	Ethanol, 2-propanol	Alcohol	1	35%, 35%	∼6	[27]
	H2O2	Microbicide	1	0.1%	≥4.5	[26]
	Sodium lauryl sulfate	Detergent	1	0.1%	≥4.6	[26]
SARS-CoV	Chloroxylenol (PCMX)	Antiseptic liquid	5	0.125%	≥6.0	[15]
	QAC (DBAC)	Dilutable cleaner	5	0.09%	≥4.8	[15]
	QAC (DBAC)	Cleaner	2	0.09%	≥3.8	[15]
	QAC (DBAC)	Pre-impregnated wipes	1.75	0.19%	≥5.8	[15]
	Citric acid	Pre-impregnated wipes	0.5	2.4%	≥3.0	[15]
MERS-CoV	Chloroxylenol (PCMX)	Antiseptic liquid	5	0.125%	≥5.0	[15]
Suspension inactivation
SARS-CoV-2	Chloroxylenol (PCMX)	Antiseptic liquid	5	0.125%	≥6.0	[15]
	Chloroxylenol (PCMX)	Antiseptic liquid	1	0.125%	≥5.0	[15]
	Chloroxylenol (PCMX)	Antiseptic	5	0.05%	≥4.8	[28]
	Chlorhexidine	Cleaner	5	0.05%	≥4.8	[28]
	Trichloroisocyanuric acid	Microbicide	0.5	1000 mg/mL	≥4.8	[29]
	QAC (DBAC)	Surface cleanser	5	0.077%	≥4.1	[15]
	QAC (BKC)	Cleaner	5	0.45%	≥4.5	[15]
	QAC (BKC)	Antiseptic	5	0.1%	≥4.8	[28]
	QAC (DNB)	Cleaner	0.5	283 mg/mL	≥4.9	[29]
	QAC (DNC)	Cleaner	0.5	283 mg/mL	≥4.9	[29]
	Lactic acid	Surface cleanser	5	1.9%	≥5.5	[15]
	Sodium hypochlorite	Dilutable cleaner	0.5	0.14%	≥5.1	[15]
	Sodium hypochlorite	Bathroom cleaner	5	0.32%	≥5.1	[15]
	Sodium hypochlorite	Household bleach	5	1:49	≥4.8	[28]
	Sodium hypochlorite	Household bleach	1	9%	≥3.3	[30]
	Hydrochloric acid	Toilet bowl cleaner	0.5	0.25%	≥4.1	[15]
	Ethanol	Disinfectant spray	5	48%	≥4.1	[15]
	Ethanol	Alcohol	5	63%	≥4.8	[28]
	Ethanol	Alcohol	0.5	30%	≥5.9	[31]
	Ethanol	Alcohol	0.5	40%	≥4.8	[29]
	Ethanol	Alcohol	5	68%	≥2.00	[30]
	2-Propanol	Alcohol	0.5	30%	≥5.9	[31]
	Copper-iodine	PPE disinfectant	30	90%	≥3.5	[32]
	Povidone-iodine	Antiseptic	5	7.5%	≥4.8	[28]
	Povidone-iodine	Antiseptic	0.5	10%	≥4.0	[33]
	Formaldehyde	Microbicide	1	10%	≥1.3	[30]
	Formaldehyde	Microbicide	15	2%	≥4.8	[34]
SARS-CoV	2-Propanol	Alcohol	0.5	80%	≥3.3	[35]
	2-Propanol	Alcohol	0.5	56%	≥3.3	[35]
	Ethanol, 2-biphenylol	Microbicide	0.5	50%, 0.16%	≥5.0	[35]
	QAC (BKC), laurylamine	Microbicide	30	0.5%	≥6.1	[36]
	QAC (BKC), glutaraldehyde	Microbicide	30	0.5%	≥3.8	[36]
	Magnesium monoperphthalate	Microbicide	30	0.5%	≥4.5	[36]
	Glutaraldehyde (ethylendioxy)dimethanol	Instrument disinfectant	15	2%	≥3.3	[36]
	Povidone-iodine	Antiseptic	1	1%	4.1	[37]
Hand hygiene agents
SARS-CoV-2	Chloroxylenol (PCMX)	Bar soap	0.5	0.014%	≥4.1	[15]
	Chloroxylenol (PCMX)	Antiseptic liquid	5	0.021%	≥4.7	[15]
	Chlorhexidine gluconate	Disinfectant	1	1.0%	3.2	[38]
	Soap	Liquid hand soap	1	90%	≥2.0	[30]
	Soap	Bar soap	0.33	8%	≥3.1	[27]
	Ethanol	Hand sanitizer gel	1	53%	≥4.2	[15]
	Ethanol	Hand sanitizer gel	1	53%	≥4.2	[15]
	Ethanol	Hand sanitizer	1	63%	≥2.5	[30]
	Ethanol	Hand sanitizer gel	0.5	70%	≥3.2	[39]
	Ethanol	Hand sanitizer foam	0.5	70%	≥3.2	[39]
	Ethanol	Hand sanitizer	0.17	65%	≥4.0	[27]
	Ethanol	Alcohol	0.08	40%	≥4.2	[38]
	2-Propanol	Alcohol	0.08	70%	≥4.2	[38]
	Salicyclic acid	Liquid gel handwash	0.5	0.025%	≥3.6	[15]
	QAC (BKC)	Foaming handwash	1	0.025%	≥3.4	[15]
	QAC (BKC)	Disinfectant	1	0.2%	3.2	[27]
	Salicyclic acid	Foaming handwash	0.5	0.023%	≥5.0	[15]
	Citric acid, lactic acid	Hand sanitizer gel	0.5	1.5%, 0.41%	≥4.7	[15]
	Povidone-iodine	Skin cleanser	0.5	7.5%	≥4.0	[33]
	Ethanol, H2O2	WHO formulation I hand rub (original)	1	72%, 0.1%	≥2.2	[30]
	Ethanol, H2O2	WHO formulation I hand rub (original)	0.5	64%, 0.1%	≥3.8	[31]
	Ethanol, H2O2	WHO formulation I hand rub (modified)	0.5	64%, 0.1%	≥5.9	[31]
	2-Propanol, H2O2	WHO formulation II hand rub (original)	0.5	60%, 0.1%	≥3.8	[31]
	2-Propanol, H2O2	WHO formulation II hand rub (modified)	0.5	60%, 0.1%	≥5.9	[31]
SARS-CoV	Ethanol, H2O2	WHO formulation I hand rub (original)	0.5	32%, 0.05%	≥5	[40]
	2-Propanol, H2O2	WHO formulation II hand rub (original)	0.5	24%, 0.04%	≥5	[40]
	2-Propanol, 1-propanol	Hand rub	0.5	36%, 24%	≥2.8	[35]
	2-Propanol, 1-propanol	Hand rub	0.5	36%, 24%	≥4.3	[35]
	Ethanol	Hand rub	0.5	64%	≥4.3	[35]
	Ethanol	Hand rub	0.5	68%	≥5.5	[35]
	Ethanol	Hand rub	0.5	76%	≥5.5	[35]
MERS-CoV	Ethanol, H2O2	WHO formulation I hand rub (original)	0.5	32%, 0.05%	≥5	[40]
	2-Propanol, H2O2	WHO formulation II hand rub (original)	0.5	32%, 0.05%	≥5	[40]
	Povidone-iodine	Surgical scrub	0.25	7.5%	4.6	[41]
	Povidone-iodine	Skin cleanser	0.25	4%	5.0	[41]
	Povidone-iodine	Scrub	1	1%	≥6.1	[41]
	Povidone-iodine	Scrub	1	0.25%	≥6.1	[41]
Sample disinfection procedures
SARS-CoV-2	Sodium dodecyl sulfate	Detergent	30	0.5%	≥4	[42]
	Sodium dodecyl sulfate	Detergent	30	10%	5.7	[34]
	Triton X-100	Detergent	30	0.5%	≥4	[42]
	Triton X-100	Detergent	30	10%	≥4.9	[34]
	NP-40	Detergent	30	0.5%	≥4	[42]
	NP-40	Detergent	30	10%	≥6.5	[34]
	Methanol	Tissue fixative	30	100%	≥6.0	[42]
	Methanol	Cell fixative	15	100%	≥6.7	[34]
	p-Formaldehyde	Tissue fixative	30	4%	≥6.0	[42]
	Formaldehyde	Cell fixative	60	10%	6	[43]
	Formaldehyde	Cell fixative	60	4%	≥7.5	[33]
	Phenol/guanidine thiocyanate	Nucleic acid extractant	5	80%	≥4	[42]
	Phenol/guanidine thiocyanate	Nucleic acid extractant	5	80%	≥4	[42]
	Phenol/guanidine thiocyanate	Nucleic acid extractant	10	0.5%	6	[43]
	Beta-propiolactone	Inactivant for vaccines	960	0.05%	6	[43]
	Polyhexamethylene biguanide	Cell lysis buffer	30	2%	1.6	[34]
SARS-CoV	Methanol	Tissue fixative	30	100%	≥6.0	[37]
	Methanol	Cell fixative	30	100%	≥6.0	[37]
	Acetone	Cell fixative	30	100%	≥6.0	[37]
	p-Formaldehyde	Tissue fixative	5	3.5%	≥3.7	[37]
	Formaldehyde	Tissue fixative	2	0.7%	≥3.0	[35]
	Glutaraldehyde	Tissue fixative	15	2.5%	≥4.4	[37]
MERS-CoV	Phenol/guanidine thiocyanate	Nucleic acid extractant	10	80%	≥6.1	[18]

Table 4.

Efficacy of microbicides for inactivating the coronaviruses SARS-CoV-2, SARS-CoV, and MERS-CoV.

^a

BKC, benzalkonium chloride; DBAC, dimethyl benzyl ammonium chloride; DBAS, dimethyl benzyl ammonium saccharinate; DNB, di-N-decyl dimethyl ammonium bromide; DNC, di-N-decyl dimethyl ammonium chloride; H₂O₂, hydrogen peroxide; MERS-CoV, Middle East respiratory syndrome coronavirus; ND, not determined; PBS, phosphate buffered saline; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; WHO, World Health Organization. Entries in blue font indicate formulations with microbicidal active ingredients.

Virus/variant^a	Active ingredients	Product type	Contact time (min)	Concentration in test	Efficacy (log10)^b	Reference(s)
Surface hygiene (steel or aluminum carriers)
Ebola Makona	Sodium hypochlorite	Microbicide	5	0.5%	≥6.6	[44]
	Sodium hypochlorite	Microbicide	5	0.5%	≥6.8	[45]
	Sodium hypochlorite	Microbicide	15	0.5%	≥2.0	[46]
	Sodium hypochlorite	Microbicide	15	0.5%	<1 (blood)	[46]
	Sodium hypochlorite	Microbicide	5	0.5%	≥5.1	[47]
	Sodium hypochlorite	Pre-impregnated wipe	0.08	1%	6.3	[48]
	Ethanol	Alcohol	5	67%	≥7.3	[44]
	Ethanol	Alcohol	2.5	70%	≥6.8	[45]
	Ethanol	Alcohol	5	70%	≥6.9	[47]
	Ethanol	Disinfectant spray	5	58%	≥4.5	[47]
	Ethanol	Pre-impregnated wipe	0.08	66.5%	6.6	[48]
	Ethanol	Alcohol	2	70%	1.7	[46]
	Ethanol	Alcohol	2	70%	<1 (blood)	[46]
	Peracetic acid	Microbicide	5	5%	≥1.0	[46]
	Peracetic acid	Microbicide	5	5%	≥2.0 (blood)	[46]
	Chloroxylenol (PCMX)	Microbicide	5	0.48%	≥5.1	[47]
	H2O2	Pre-impregnated wipe	1	2.5%	6.4	[48]
	H2O2, peroxyacetic acid	Microbicide	5	Undiluted	2.6	[46]
	H2O2, peroxyacetic acid	Microbicide	5	Undiluted	<1 (blood)	[46]
	QAC	Microbicide	10	1.5%	<1	[46]
	QAC	Pre-impregnated wipe	1	As supplied	6.6	[48]
	QAC	Pre-impregnated wipe	0.08	5%	6.0	[48]
Ebola Mayinga	Sodium hypochlorite	Microbicide	5	0.5%	≥6.6	[45]
	Ethanol	Alcohol	1	70%	≥6.6	[45]
Ebola Kikwit	Sodium hypochlorite	Microbicide	5	0.5%	≥6.5	[45]
	Ethanol	Alcohol	1	70%	≥6.5	[45]
Ebola Yambuku-Ecran	Sodium hypochlorite	Microbicide	10	0.75%	≥6.5	[49]
	Alcohol formulation	Microbicide	10	50%	5.3	[42]
	QAC, alcohol	Microbicide	10	1.5%	2.5	[42]
	QAC, alkylamine	Microbicide	10	2.5%	4.2	[42]
Suspension inactivation
Ebola Makona	Chloroxylenol (PCMX)	Antiseptic liquid	1	0.48%	≥4.8	[50]
Ebola Zaire	Povidone-iodine	Microbicide	0.25	1:10+	≥5.5	[51]
Hand hygiene agents
Ebola Makona	Salicylic acid, citric acid	Liquid hand wash	0.5	1:4	4.8	[52]
Ebola Zaire	Povidone-iodine	Skin cleanser	0.5	1:10	≥4.5	[51]
	Povidone-iodine	Surgical scrub	0.25	1:10	≥5.5	[51]
	Povidone-iodine, alcohol	Skin cleanser	0.25	Undiluted	≥5.7	[51]
Ebola Mayinga	Ethanol, H2O2	WHO formulation I hand rub (original)	0.5	32%, 0.05%	≥5	[40]
	2-Propanol, H2O2	WHO formulation II hand rub (original)	0.5	24%, 0.04%	≥5	[40]
Sample disinfection procedures
Ebola	Triton X-100	Detergent	60	0.1%	4	[53]
Ebola Makona	Triton X-100	Detergent	60	0.1%	≥3 (FBS)	[54]
	Phenol/guanidine thiocyanate	Nucleic acid extractant	10	80% of neat	≥5.5	[19]
	Sodium dodecyl sulfate	Detergent	60	0.1%	≥3 (FBS)	[54]
	Sodium dodecyl sulfate	Detergent	60	0.1%	∼1 (blood)	[54]
Ebola Sudan	Phenol/guanidine thiocyanate	Nucleic acid extractant	10	80% of neat	≥4.5	[19]
Ebola Mayinga	Acetic acid	Sample inactivant	15	3% (pH 2.5)	≥3 (blood)	[18]
Marburg Ci67	Phenol/guanidine thiocyanate	Nucleic acid extractant	10	80% of neat	≥6.1	[19]
Marburg Musokee	Acetic acid	Sample inactivant	15	3% (pH 2.5)	≥3	[18]

Table 5.

Efficacy of microbicides for inactivating the filoviruses Ebola and Marburg viruses.

^a

FBS, fetal bovine serum; H₂O₂, hydrogen peroxide; QAC, quaternary ammonium compound; WHO, World Health Organization. Entries in blue font indicate formulations with microbicidal active ingredients.

^b

Inactivation matrix was virus stock (virus in culture medium), unless otherwise indicated.

Virus/strain	Active ingredient	Product type	Contact time (min)	Concentration in test	Efficacy (log10)	Reference(s)
Surface hygiene (glass or plastic carriers)
Zika virus PRVABC59	2-Propanol	Alcohol	0.25	70%	≥5.1	[55]
					≥5.6 (blood)	[55]
	QACa/2-propanol	Microbicide	0.25	Undiluted	≥3.5	[55]
					≥3.4 (blood)	[55]
	Peracetic acid	Microbicide	5	1000 ppm	≥4.9	[55]
					1.4 (blood)	[55]
	Chlorine	Microbicide	5	500 ppm	≥4.1	[55]
					0.1 (blood)	[55]
Zika virus MR 766	Sodium hypochlorite	Microbicide	1	1%	>3	[56]
	Ethanol	Commercial alcohol	1	70%	>3	[56]
	2-Propanol	Commercial alcohol	1	70%	>3	[56]
	Paraformaldehyde	Microbicide	1	2%	>3	[56]
	Glutaraldehyde	Tissue fixative	1	2%	>3	[56]
Suspension inactivation
Zika virus MR 766	Sodium hypochlorite	Microbicide	1	0.70%	>6	[56]
	Ethanol	Microbicide	1	49%	>6	[56]
	2-Propanol	Microbicide	1	49%	>6	[56]
	Paraformaldehyde	Microbicide	1	1.4%	>6	[56]
	Glutaraldehyde	Tissue fixative	1	1.4%	>6	[56]
Hand hygiene agents
Zika virus MP 1751	Ethanol, H2O2	WHO formulation I hand rub (original)	0.5	32%, 0.05%	≥5	[40]
	2-Propanol, H2O2	WHO formulation II hand rub (original)	0.5	24%, 0.05%	≥5	[40]
Sample disinfection procedures
Zika virus PRVABC59	β-Propiolactone	Microbicide	180	3%	>7	[57]
	Ethanol	Alcohol	5	35%	>7	[57]
	Ethanol	Alcohol	2	58%	>7	[57]
	QAC^a	Microbicide	2	2.5%	>7	[57]
	QACa	Microbicide	1	4.2%	>7	[57]
	QACa	Microbicide	2	50%	>7	[57]

Table 6.

Efficacy of microbicides for inactivating the flavivirus Zika virus.

^a

QAC, quaternary ammonium compound: n-alkyl dimethyl benzyl ammonium chloride, n-alkyl ethyl benzyl ammonium chloride; H₂O₂, hydrogen peroxide; WHO, World Health Organization. Entries in blue font indicate formulations with microbicidal active ingredients.

Virus/strain^a	Active ingredient	Product type	Contact time (min)	Concentration in test	Efficacy (log10)	Reference(s)
Surface hygiene
No literature found
Suspension inactivation
No literature found
Hand hygiene agents
No literature found
Sample disinfection procedures
Nipah	Phenol/guanidine thiocyanate	Sample inactivant	10	80% of neat	≥6.0	[19]

Table 7.

Efficacy of microbicides for inactivating the paramyxoviruses Nipah virus and other henipaviruses.

Not all of the virucidal efficacy information from the reviewed articles is shown in Tables 2–7. Wherever possible, the virucidal efficacy data shown are from conditions leading to the highest log₁₀ reduction level, or complete-inactivation of the challenge virus to the limit of detection of the infectivity assays used. No data from studies using exclusively nucleic acid assays have been included, as the nucleic acid endpoints are not useful for measuring infectious virus unless integrated cell culture-qPCR based assays [58] are used. The individual reports in papers referenced in this chapter should be consulted for complete information, including concentration/response information, time/inactivation kinetics information, and microbicidal product names (which have not been included here).

4.1 Lassa virus

There have appeared in the literature only few reports of the empirical testing of microbicides for efficacy as virucides for the arenavirus (Lassa virus). The literature that has been identified has been summarized in Table 2. In addition, some descriptions of the utility of microbicides can be found in the secondary literature. For example [59], “LASV [Lassa virus] is susceptible to inactivation by most detergents and disinfectants. Sodium hypochlorite (0.5–1%), phenolic compounds, 3% acetic acid, lipid solvents and detergents (e.g., SDS), formaldehyde/paraformaldehyde, glutaraldehyde (2%), and beta-propiolactone disrupt virion integrity.” The source provided for these claims was another secondary source [60]. No primary literature source was provided for these claims, and it should be noted that important information such as contact times, temperatures, inactivation matrices, or methodologies was not provided in these secondary sources [59, 60].

No primary literature (peer-reviewed) for virucidal efficacy of Lassa virus by microbicides on surfaces or in suspensions, or for efficacy of hand hygiene agents was identified during this literatures search. Characterization of the efficacy of microbicides for these purposes is required to resolve this knowledge gap. The few reports found related to agents intended for rendering laboratory samples safe for use in diagnostic assays [18, 19, 20, 21].

4.2 Crimean-Congo hemorrhagic fever virus and Rift Valley fever virus

There are few reports of the empirical testing of microbicides for efficacy as virucides for the bunyaviruses [Crimean-Congo hemorrhagic fever virus (CCHFV) and Rift Valley fever virus (RVFV)]. The literature that has been identified has been summarized in Table 3. In addition, some descriptions of disinfectant utility can be found in the secondary literature. For example, “CCHFV can be inactivated by many disinfectants including 1% hypochlorite, 70% alcohol, hydrogen peroxide, peracetic acid, iodophors, glutaraldehyde, and formalin” [61]. No primary literature source was provided for these claims, and it should be noted that important information such as contact times, temperatures, inactivation matrices, or methodologies was not provided in this brief description [61]. Similar information is provided in the review by Bartoli et al. [62]. In that review, which has an emphasis on laboratory safety, attribution to the primary literature for CCHFV is provided for one of the eight references supporting the disinfectant efficacy section. The remaining references are either secondary literature or are related to the filovirus Ebola virus, not to CCHFV. Thus, the same disinfectant efficacy data, for which primary supporting data do not appear to be available, have appeared in numerous secondary sources and review articles on RVFV or CCHFV.

No primary reports describing efficacy of microbicides as surface or hand hygiene agents, or for inactivating these viruses in suspensions were identified during the literature search (Table 3). This represents a significant knowledge gap with respect to IPAC for these viruses. The available inactivation efficacy data relate to vaccine virus inactivation [22, 23] and sample disinfection reagents/cell fixatives [19, 21, 24, 25] for RVFV or CCHFV. The few microbicides that have been evaluated are solvents or detergents with expected efficacy for inactivating an enveloped virus, such as a bunyavirus.

4.3 SARS-CoV-2, SARS-CoV, and MERS-CoV

In the case of SARS-CoV-2, an extensive literature for virucidal efficacy of microbicides has been developed over the past year and a half. To a lesser extent, literature for original SARS-CoV and for MERS-CoV was identified. Data on the inactivation of these beta-coronaviruses by microbicides are summarized in Table 4. The information displayed in Table 4 considers microbicides intended for disinfection of HITES [15, 26, 27], inactivation in liquid suspension [15, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37], and microbicides intended for hand hygiene [15, 27, 30, 31, 33, 35, 38, 39, 40, 41, 63] and for laboratory sample decontamination [19, 34, 35, 37, 42, 43]. Additional reports on disinfection of laboratory samples which did not report results in terms of log₁₀ reduction in titer include the following [64, 65]. The inactivation literature for SARS-CoV-2 and other coronaviruses has been reviewed extensively [66, 67, 68, 69, 70, 71, 72, 73, 74, 75]. Readers interested in the virucidal efficacy of these microbicides for coronaviruses under different testing conditions, carrier types, contact times, temperatures, and the presence or absence of a challenge soil load are advised to examine these review papers, as well as the primary literature sources indicated in Table 4. It was not possible to display all useful information from these sources within one summary table, so Table 4 should be used as a guide for pursuing additional detail for the listed microbicides and applications.

The types of microbicides that display virucidal efficacy for SARS-CoV-2, SARS-CoV, and MERS-CoV-2 are those expected to be lipid-disrupting agents (e.g., solvents, alcohols, detergents, phenolics, and quaternary ammonium compounds) and broad-spectrum microbicides (oxidizing agents, and organic and inorganic acids and bases). Inactivation conditions leading to complete inactivation to the limit of detection of the infectivity assays have been described in Table 4, enabling researchers and healthcare workers to implement cleaning regimens with the greatest chances of limiting onward transmission of the virus through contaminated fomites, solutions, hands, and diagnostic samples. The primary knowledge gap identified during this literature review is around the efficacy of plain soap and water inactivation of the beta-coronaviruses. This gap has been discussed previously [76].

4.4 Ebola virus and Marburg virus

Ebola virus and Marburg virus are members of the Filoviridae family. These are enveloped viruses which cause relatively lethal hemorrhagic fevers in humans. Most of the available literature on inactivation of Ebola virus variants by microbicides has been generated in carrier studies [44, 45, 46, 47, 48, 49]. Very little data for inactivation of Ebola virus in suspension studies was identified during the literature search [50, 51]. Few reports of the efficacy of hand hygiene agents for inactivating Ebola virus were found [40, 51, 52], while efficacy of laboratory sample decontamination agents has been reported both for Ebola virus variants [18, 19, 53, 54] and Marburg virus strains [18, 19]. The data from these reports have been summarized in Table 5. Fortunately, a variety of Ebola variants have been used as challenge viruses, and at least two strains of Marburg virus have been evaluated. Where side-by-side comparisons of efficacy between variants has been evaluated [45], any differences in virucidal efficacy identified have been relative; that is, differences have been in degree of inactivation (i.e., log₁₀ reduction in titer) only.

Knowledge gaps for Ebola virus inactivation include evaluation of the efficacy of plain soap and water hand washing. In the case of Marburg virus, little virucidal-efficacy data of microbicides (surface and hand hygiene agents) have been generated. This knowledge gap is, therefore, relatively profound. The secondary literature [77] suggests that “Ebola viruses and Marburg viruses are both reported to be susceptible to sodium hypochlorite, glutaraldehyde, β-propiolactone, 3% acetic acid (pH 2.5), formaldehyde, and paraformaldehyde. Recommended dilutions of sodium hypochlorite may vary with the use. Calcium hypochlorite, peracetic acid, methyl alcohol, ether, sodium deoxycholate, and some other agents have also been tested against Ebola viruses, and found to be effective.” The only source provided in support of the above was Mitchell and McCormick [18]. As is apparent, much of the current knowledge in such secondary sources [77, 78] pertains to inactivating agents for rendering laboratory samples safe for use. It should be noted that for most of the listed microbicides, important information such as microbicide concentration, contact time, temperature, inactivation matrix, or study methodology was not provided in these secondary sources.

4.5 Zika virus

Zika virus is a member of the Flaviviridae family of enveloped viruses, which includes such common pathogens as hepatitis C virus, West Nile virus, hog cholera virus, and bovine viral diarrhea virus. Data on the inactivation of Zika virus by microbicides have been summarized in Table 6. The information displayed in Table 6 considers microbicides intended for surface disinfection [55, 56], inactivation in liquid suspension [56], and microbicides intended for hand hygiene [40], and for laboratory sample decontamination [57]. While the totality of the data is relatively minimal, a variety of lipid-disrupting agents have been evaluated and found effective. The oxidizing agents (chlorine, sodium hypochlorite, and hydrogen peroxide) also proved effective, as expected per the hierarchy of susceptibility to microbicides (Figure 1). Note that the peracetic acid- and chlorine-containing microbicides displayed limited efficacy when the virus was dried on carriers within a blood matrix (Table 6). Since Zika virus is transmitted primarily through insect vectors and fomite (indirect) transmission plays a lesser role, the surface hygiene, suspension inactivation, and hand hygiene efficacy data are mainly relevant to IPAC under health-care and laboratory settings (i.e., handling clinical samples containing bodily fluids for analysis). Relevance for the public-at-large is perhaps lesser, compared with the other viruses discussed within this chapter.

4.6 Nipah virus and other henipaviruses

Very little information on the virucidal efficacy of microbicides for Nipah virus or other henipaviruses was identified during this literature search. Claims as to utility of certain microbicides for these paramyxoviruses include the following: “Paramyxoviruses are susceptible to common soaps and disinfectants; lipid solvents (alcohol and ether) and sodium hypochlorite solutions were used effectively in outbreaks for cleaning and disinfection” [79]. This sort of information, without supporting primary literature, is only marginally useful. Important information, including microbicide concentration, contact time, matrix and methodology used to determine virucidal efficacy, are missing from this brief statement. It is clear from Table 7 that considerable knowledge gaps exist for virucidal efficacy of microbicides for these Priority List paramyxoviruses.

5. Discussion

In the case of IPAC, it is common for microbicidal actives to be formulated into products intended for surface or hand hygiene. These products are used to interrupt the cycle of infection involving the indirect transfer of virus from contaminated fomites to the hand and then to mucous membranes of a susceptible individual. There is also the possibility of re-aerosolization of virus from a contaminated fomite [80, 81, 82, 83, 84], potentially leading to direct airborne transmission to mucous membranes of a susceptible person. As mentioned in the preceding sections, these routes of infection may be less important for those viruses that are primarily transmitted through insect vectors (e.g., Zika virus). Microbicides are typically used for all of the WHO Priority List viruses as is for disinfection of laboratory samples to render them safe for handling.

The stated purpose of this review was to identify gaps in the current state of the science regarding the virucidal efficacy of microbicides (including surface and hand hygiene agents) for viruses causing the current WHO Priority List diseases. The viruses that cause Priority List diseases are also mentioned in lists of pathogens of concern issued by other health agencies globally. For instance, Lassa virus, Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, Ebola virus, and Marburg virus are also mentioned in the National Institute of Allergy and Infectious Diseases (NIAID) Emerging Infectious Diseases/Pathogens priority A list [85]. The NIAID list was issued in 2018 and, therefore, did not include SARS-CoV-2. SARS-CoV-2 is certainly now a priority virus for NIAID [86]. A discussion of emerging and re-emerging viruses can be found in Morens and Fauci [87]. Listed among other emerging viruses in that review are SARS-CoV, MERS-CoV, SARS-CoV-2, Zika virus, Rift Valley fever virus; Nipah virus, Hendra virus, Ebola virus, and Marburg virus. Additional viruses not mentioned in the WHO Priority List include additional bunyaviruses, influenza virus strains, enteroviruses and poxviruses [87]. A recent review of emerging and re-emerging viral infections by Schwartz [88] also mentions, among other viruses, Lassa virus, Ebola virus, Marburg virus, Zika virus, SARS-CoV-2, MERS-CoV, and SARS-CoV, and Rift Valley fever virus. Knowledge gaps outlined in that review did not include gaps in information on disinfection/surface hygiene and hand hygiene. The WHO also maintains what is referred to as an “R&D Blueprint” and an “R&D Roadmap” to provide guidance on appropriate responses to Priority List disease outbreaks and to develop ways to improve global responses to future epidemics [89]. This was last updated in 2017 and, therefore, is not as current as the WHO Priority List. The R&D Blueprint also is more a description of the types of knowledge gaps for epidemic preparedness (vaccine testing, diagnostic technologies, therapeutic interventions, vector control) than a list of viruses of concern [89].

It was assumed at the time of undertaking this literature review that, by definition, information would be minimal for at least some of the Priority List viruses (Table 1), and this indeed turned out to be the case. Although it is clear that knowledge for one member of a given virus family should be informative for other members of the same virus family, the purpose of this review was to identify knowledge gaps for the specific viruses of concern, not to review inactivation information for surrogate viruses from the same or other viruses from the families (Table 1). Such an exercise, while of value for IPAC of these specific viruses, was considered to be well beyond the scope of this chapter. Readers interested in identifying microbicides with efficacy for inactivating any of the Priority List viruses are encouraged to review the literature cited in this chapter, to consider the predictions of virucidal efficacy discussed in Section 3 of this chapter, and to search and review the literature for inactivation of other members of the virus family of interest.

It can be safely said that, following these steps, one may arrive at a list of microbicides and conditions (temperature, microbicide concentration, contact time, testing matrix, etc.) that should adequately inactivate each of the Priority List viruses. As an example, there are extremely limited data for the paramyxoviruses Nipah virus and other henipaviruses. There are, however, a variety of other paramyxoviruses for which inactivation data are available, and the lipid-disrupting agents and broad-spectrum microbicides effective against the less lethal paramyxoviruses (e.g., respiratory syncytial virus, parainfluenza virus type 3) should be equally effective against the Priority List paramyxoviruses.

It is clear that during the ongoing SARS-CoV-2 pandemic, the majority of the resources of the public health community were applied to research into one or more of the many different aspects of SARS-CoV-2 for IPAC. In fact, many laboratories have been conducting research exclusively on SARS-CoV-2 during the ongoing pandemic. Because of this, literature on all aspects of the virus and the disease, COVID-19, has appeared on a relatively continuous basis. The relatively great amount of empirical data collected to date on the virucidal efficacy of microbicides for SARS-CoV-2, SARS-CoV, and MERS-CoV (Table 4) reflects this emphasis. Of course, during a pandemic impacting ∼435 million confirmed cases globally and ∼5.9 million global deaths as of February 28, 2022 [90], this universal focus on the virus and the disease was, and remains, appropriate, particularly with the emergence of Delta, Omicron, and other variants [91, 92].

It is also clear from this review of the literature on the virucidal efficacy of microbicides for the WHO Priority List viruses that relatively limited information is available on some viruses, especially the paramyxoviruses Nipah virus and related henipaviruses and the bunyaviruses CCHFV and RVFV. Rift Valley fever virus and CCHFV are infectious agents considered as bioterrorism threats, due in part to the paucity of knowledge on measures for mitigating the transmission of the viruses and severity of the associated diseases [93, 94]. Reviews of focus areas and knowledge gaps for CCHFV [93, 94, 95] mention tick (vector) surveillance and vector control agents, but does not discuss knowledge gaps around surface disinfection or hand hygiene. For the arboviruses (Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, Zika virus), the possibility of contamination of high-touch environmental surfaces with patient blood spills and other patient excretions/secretions needs to be considered and transmission risk mitigated through application of effective microbicides. Further research into this topic is, therefore, required. For surface virucidal studies, the impact of the matrix in which the challenge virus is suspended at time of drying on the carrier should always be evaluated. As shown in the Zika surface inactivation studies (Table 6), virus deposited in a blood matrix does not appear to be effectively inactivated by the microbicides peracetic acid and chlorine, compared to inactivation of virus dried in the absence of the blood load [55].

It is to be expected that, as the current pandemic wanes, research into the more lethal, albeit less common, viral diseases mentioned in this chapter will be encouraged and undertaken at the BSL-3 and BSL-4 laboratories capable of safely handling these viruses. For instance, further studies need to be carried out on the virucidal efficacy of commonly used microbicides (surface and hand hygiene agents) for Lassa virus and Nipah virus in surface and suspension inactivation studies. This information will provide additional confirmation of the expectation that microbicides capable of inactivating enveloped viruses, in general, should be effective for these Priority List viruses. Until such data are generated, the IPAC community will continue to be able to leverage virucidal efficacy data for other enveloped and non-enveloped viruses per the Emerging Viral Pathogen Guidance for Antimicrobial Pesticides from the U.S. EPA [4, 5] and the European tiered approach for virucidal efficacy testing [96].

6. Conclusions

In this chapter, we have reviewed the current state of the science regarding the virucidal efficacy of microbicides for viruses causing the current WHO Priority List diseases. By definition, information might be expected to be minimal for at least some of these viruses, hence the need for encouraging additional research. Not surprisingly, the efficacy of microbicides for inactivation of certain of the lethal (BSL-4) viruses, especially the paramyxoviruses Nipah virus and related henipaviruses and the bunyaviruses CCHFV and RVFV, was found to be poorly characterized. The need for further research into the virucidal efficacy of microbicides for the arenavirus (Lassa virus) and the filovirus (Marburg virus) is also indicated by the relative paucity of empirical data identified during the review. For the beta-coronaviruses (SARS-CoV, SARS-CoV-2, and MERS-CoV), the filovirus (Ebola virus), and the flavivirus (Zika virus), the available knowledge base for virucidal efficacy of microbicides appears to be adequate for verifying the predicted efficacy based on the hierarchy of virus susceptibility to microbicides.

It is hoped that this discussion will provide assurance to the IPAC community of the empirically determined virucidal efficacy of targeted hygiene agents against SARS-CoV-2 for use during the current SARS-CoV-2/COVID-19 pandemic. SARS-CoV-2 is evolving continuously, and the emerging mutational variants are being monitored for impact on previously vaccinated and non-vaccinated individuals. The microbicides displaying virucidal efficacy against SARS-CoV-2, MERS-CoV, and SARS-CoV should display equivalent efficacy against emerging mutational variants [97], including the Delta, Omicron, and other variants. Current Variants of Interest (VOI) may become Variants of Concern (VOC) in the future, and the appropriate CDC/WHO websites [91, 92] should be consulted to keep up-to-date regarding the mutational variants of SARS-CoV-2. The information presented in this chapter also should be useful for the IPAC community as it considers non-pharmaceutical interventions for the other Priority List diseases in addition to SARS-CoV-2.

Acknowledgments

The authors thank Drs. Chris Jones and Mark Ripley, Reckitt Benckiser R&D, for their critical review of the manuscript.

Conflict of interest

Drs. Julie McKinney and M. Khalid Ijaz are engaged in R&D at Reckitt Benckiser LLC. Dr. Raymond W. Nims is employed by RMC Pharmaceutical Solutions, Inc. and received a fee from Reckitt Benckiser LLC for his role in authoring and editing the manuscript. Reckitt Benckiser LLC participated in the decision to publish.