A Comprehensive Review on the Efficacy of Several Pharmacologic Agents for the Treatment of COVID-19

Abstract

SARS-CoV-2, the coronavirus disease-2019 (COVID-19), and the cause of the pandemic is extremely contagious among people and has spread around the world. Antivirals, immunomodulators, and other medications, such as antibiotics, stem cells, and plasma therapy, have all been utilized in the treatment of COVID-19. To better understand the clinical efficacy of these agents and to aid in the selection of effective COVID-19 therapies in various countries, this study reviewed the effectiveness of the various pharmacologic agents that have been used for COVID-19 therapy globally by summarizing the clinical outcomes that have been obtained from the clinical trials published on each drug related to COVID-19 infection. The Food and Drug Administration (FDA) has authorized the use of remdesivir, paxlovid, molnupiravir, baricitinib, tixagevimab–cilgavimab, and bebtelovimab for the management of COVID-19. On the other hand, most research advises against using chloroquine and hydroxychloroquine to treat COVID-19 patients because they are not beneficial. Although the FDA has given emergency use authorization for some monoclonal antibodies, including bamlanivimab, etesevimab, casirivimab, and imdevimab for managing COVID-19, they are not currently approved for use because the Omicron variant has significantly reduced their in vitro susceptibility. In this study, we also included a wide range of alternative therapy strategies that effectively treat COVID-19 patients, although further randomized studies are necessary to support and assess their applicability.

Antiviral activity of Molnupiravir precursor NHC against SARS-CoV-2 Variants of Concern (VOCs) and implications for the therapeutic window and resistance

“…Anti-virals can target either specific viral proteins or act non-specifically across the viral genome. Three anti-virals for SARS-CoV-2 have been licensed in the UK: Nirmatrelvir/Ritonavir (Paxlovid), Remdesivir and Molnupiravir (Haddad et al, 2022), each with their own advantages and disadvantages.…”

Molnupiravir: A Versatile Prodrug against SARS-CoV-2 Variants

“…AGILE CST-2 (NCT04746183) was a phase 2 clinical trial that evaluated the safety and effectiveness of molnupiravir in individuals who had received COVID-19 vaccinations [ 107 ]. The study included 180 participants, with an average age of 43 years and approximately equal numbers of males and females.…”

“…In contrast, 73 of the 90 molnupiravir participants had at least one adverse event by day 29. This trial suggests that molnupiravir may be safe for use in individuals who have received COVID-19 vaccinations, although further research is needed to fully understand its potential therapeutic effects [ 107 ].…”

A Clinical Insight on New Discovered Molecules and Repurposed Drugs for the Treatment of COVID-19

“…Molnupiravir was found effective at higher doses when compared with others (400 and 800 mg BID oral dose) [ 14 , 21 , 22 , 24 ]. Although only 6.8% death or hospitalization case was reported for molnupiravir, the mutation of the patient’s DNA is a significant adverse effect [ 91 ]. On the other hand, only a negligible difference was observed between molnupiravir and placebo for other adverse events.…”

“…Unlike molnupiravir, Paxlovid™ did not cause any mutation in host DNA [ 35 ]. Molnupiravir inhibits RdRp to block the viral transcription, while Paxlovid™ (especially nirmatrelvir) is a protease inhibitor and acts on the 3-chymotrypsin-like cysteine protease enzyme (M pro ) [ 91 ]. Pharmacokinetic parameters of nirmatrelvir increases when administered with ritonavir due to CYP3A4 inhibition, leading to a reduction in the metabolism of nirmatrelvir [ 93 ].…”