Oral antivirals for the prevention and treatment of SARS-CoV-2 infection

Abstract

Vaccines and antivirals are the classical weapons deployed to contain, prevent, and treat life-threatening viral illnesses. Specifically, for SARS-CoV-2 infection, vaccines protect against severe COVID-19 disease manifestations and complications. However, waning immunity and emergence of vaccine escape mutants remains a growing threat. This is highlighted by the current surge of the omicron COVID-19 variant. Thus, there is a race to find treatment alternatives. We contend that oral small molecule antivirals that halt SARS-CoV-2 infection are essential. Compared to currently available monoclonal antibodies and remdesivir, where parenteral administration is required, oral antivirals offer treatments in an outpatient setting with dissemination available on a larger scale. In response to this need at 2021's end, regulatory agencies provided emergency use authorization for both molnupiravir and nirmatrelvir. These medicines act on the viral polymerase and protease, respectively. Each is given for 5 days and can reduce disease progression by 30% and 89%, respectively. The advent of additional oral antivirals, the assessment of combination therapies, the formulation of extended-release medications, and their benefit for both early treatment and prophylaxis will likely transform the landscape of the COVID-19 pandemic.

Real-world effectiveness of early molnupiravir and nirmatrelvir/ritonavir among hospitalized, non-oxygen-dependent COVID-19 patients on admission during Hong Kong’s Omicron BA.2 wave: an observational study

“…Secondly, our results could potentially be biased considering clinical contraindications by drug-drug interactions for nirmatrelvir/ritonavir, or patient preferences to avoid molnupiravir due to concerns about possible mutagenicity on fertility or pregnancy. 43 However, our analysis excluded patients with drug contraindications to nirmatrelvir/ritonavir, and those with severe renal or liver diseases for fair comparisons between oral antiviral users and matched controls. Thirdly, since the Ct value was no longer adopted as one of the discharge criteria during our study period, patients might have already been deemed clinically stable for discharge before reaching the specific cutoff.…”

Berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking S protein-mediated membrane fusion

“…Molnupiravir, a potent RNA-dependent RNA polymerase inhibitor, is the first approved oral antiviral agent for treating COVID-19. Ritonavir in combination with PF-07321332 was approved for emergency use by the US Food and Drug Administration on 22 December 2021 for the treatment of mild-to-moderate COVID-19 disease [ 2 ]. However, the severity of the ongoing global pandemic still urges the efforts to discover new antiviral compounds.…”

SARS‐CoV‐2 and its variants of concern including Omicron: A never ending pandemic

“…Vaccines and antivirals protect the people against severe COVID‐19 disease manifestations and complications. In this context, the emergency use of two antivirals, namely, molnupiravir and nirmatrelvir, has been approved, which may reduce disease progression by 30% and 89%, respectively, with 5 days use (Soriano et al, 2022 ). The commonly used drugs, their mechanism of action, and clinical trial results are also reported in Table 1 .…”

“…A number of repurposing drugs and steroids are commonly used to treat the disease. However, some serious side effects are observed as listed in (Soriano et al, 2022). The commonly used drugs, their mechanism of action, and clinical trial results are also reported in Table 1.…”