Perspectives for antivirals to limit SARS-CoV-2 infection (COVID-19)

Abstract

Compared with vaccines, antivirals for curbing COVID-19 (SARS-CoV-2 infection) have been developed at a much lower pace. Favipiravir has proven efficacious (in hamsters) but only at a very high dose which may not be feasible in humans. Remdesivir is the sole antiviral approved by the US FDA, but it has not been extensively evaluated for its safety.EIDD-1931 and EIDD-2801 have not been evaluated clinically. M pro (protease) inhibitors likewise need to be subjected to clinical efficacy and safety studies. Remdesivir is a C-nucleoside and this class of compounds should be further evaluated.Polyanionic substances interfering with virus adsorption to the host cells have not been explored. They may possibly be administered by inhalation. Corticosteroids (such as dexamethasone), while virus-stimulating rather than inhibitory, may counteract the 'cytokine storm'. Combination of (two or more of) the compounds mentioned above may offer an increased benefit through a synergistic interaction.

Reflections on the COVID-19 pandemic from a university academic

“…Despite some protection via herd immunity, we need to continue research on efficacious drugs that can be used to treat COVID-19. The progress on COVID-19 drugs was recently reported in two Microbiology Australia articles 8,9 .…”

Hydrogen Bonding (Base Pairing) in Antiviral Activity

“…Remdesivir (GS-5734) is a prodrug of a C-nucleoside ( Figure 9 A) with a purine moiety reminiscent of adenine, which explains why it is able to base-pair with uracil ( Figure 9 B). After COVID-19 emerged, remdesivir has been granted special approval (as Veklury ® ) for the treatment of SARS-CoV-2 infections [ 40 ].…”

“…Remdesivir (GS-5734) is a prodrug of a C-nucleoside (Figure 9A) with a purine moiety reminiscent of adenine, which explains why it is able to base-pair with uracil (Figure 9B). After COVID-19 emerged, remdesivir has been granted special approval (as Veklury ® ) for the treatment of SARS-CoV-2 infections [40]. The C-nucleoside part of remdesivir originally featured among a series of 1′-substituted 4-aza-7,9-dideazaadenosine C-nucleosides [41], which showed a broad range of antiviral effects, particularly against HCV (hepatitis C virus).…”