Chapters authored
Resistance to Direct-Acting Antiviral Agents in Treatment of Hepatitis C Virus Infections
Compounds targeting nonstructural (NS) proteins of hepatitis C virus (HCV) demonstrate clinical promise, suggesting that NS3/NS4a, NS5A, or NS5B inhibitors are potential components in direct-acting antiviral (DAA) combination therapies. In vitro studies revealed dramatic inhibition of viral replication or alteration in subcellular localization of NS proteins. DAAs bind either to catalytic sites (NS3 and NS5B) or to domain-1 of NS5A. Although >90% of the patients clear HCV RNA from their sera, a significant portion of cirrhotic patients suffer from resistance or virological relapse. Mutations in specific residues (Q80K) in NS3 (M28, A30, L31, and Y93 in genotypes 1a and 1b or L28, L30, M31, and Y93 in genotype 4) in NS5A and A282T in NS5B are associated with resistance to DAA [resistance-associated variants (RAVs)]. Current knowledge on the NS functions, mode of action of DAAs, and impacts of RAVs on treatment response are discussed. Not only mutations affecting the binding of DAAs to target proteins but also substitutions affecting the replication fitness of mutant quasispecies are major determinants of treatment failures. These resistance-associated substitutions (RASs) are now considered the major viral mutants that influence the virological outcome after DAA treatment.
Part of the book: Update on Hepatitis C
Therapeutic Interventions for COVID-19
SARS-CoV-2, a novel coronavirus, is currently represented a major public health concern. The high transmission rate of this virus increases the mortality rate worldwide. To date, significant efforts and restricted regulations were performed around the world to control this crisis effectively, but unfortunately, there is no specific and successful therapy for COVID-19. Many approaches have been repurposed for SARS-CoV-2 treatment such as antivirals and anti-inflammatories. Furthermore, antibody therapies are one of the main and important approaches of SARS-CoV-2 infection treatment. In recent trials, various immunotherapeutic interventions such as convalescent plasma therapy and monoclonal antibodies, as well as immunomodulatory agents are being proposed. However, the development of a vaccine that provides durable protective immunity will be the most effective therapy for controlling possible epidemics of this virus. The current review summarized all the proposed therapeutic approaches together with information on their safety and efficacy in treating COVID-19, as well as the vaccine candidates. The provided comprehensive information regarding the applied therapeutic strategies against COVID-19 might help the scientific community in any progress toward the treatment of COVID-19 infection.
Part of the book: Post COVID-19