Navigating the COVID-19 Therapeutic Landscape: Unveiling Novel Perspectives on FDA-Approved Medications, Vaccination Targets, and Emerging Novel Strategies

Abstract

Amidst the ongoing global challenge of the SARS-CoV-2 pandemic, the quest for effective antiviral medications remains paramount. This comprehensive review delves into the dynamic landscape of FDA-approved medications repurposed for COVID-19, categorized as antiviral and non-antiviral agents. Our focus extends beyond conventional narratives, encompassing vaccination targets, repurposing efficacy, clinical studies, innovative treatment modalities, and future outlooks. Unveiling the genomic intricacies of SARS-CoV-2 variants, including the WHO-designated Omicron variant, we explore diverse antiviral categories such as fusion inhibitors, protease inhibitors, transcription inhibitors, neuraminidase inhibitors, nucleoside reverse transcriptase, and non-antiviral interventions like importin α/β1-mediated nuclear import inhibitors, neutralizing antibodies, and convalescent plasma. Notably, Molnupiravir emerges as a pivotal player, now licensed in the UK. This review offers a fresh perspective on the historical evolution of COVID-19 therapeutics, from repurposing endeavors to the latest developments in oral anti-SARS-CoV-2 treatments, ushering in a new era of hope in the battle against the pandemic.

Keywords: SARS-CoV-2; drug repurposing; molnupiravir; paxlovid; vaccines; variant of concerns (VOC).

Figure 1

Schematic diagram for vaccine candidates in human trial. Created with Biorender. The timeline could reflect key milestones in the development, approval, and rollout of COVID-19 vaccines across different platforms, highlighting significant events. January 2020: Identification of SARS-CoV-2 and global initiation of vaccine research. March 2020: Start of clinical trials for multiple vaccine platforms (e.g., mRNA, adenovirus vector, protein subunit). December 2020: Emergency Use Authorization (EUA) of Pfizer-BioNTech (Comirnaty) and Moderna (Spikevax) mRNA vaccines in the United States and Europe. February 2021: EUA for Johnson & Johnson’s adenovirus vector vaccine. March 2021: WHO Emergency Use Listing (EUL) for AstraZeneca (Vaxzevria) adenovirus vector vaccine. July 2021: Full FDA approval of Pfizer-BioNTech vaccine (Comirnaty) for individuals aged 16+. November 2021: Booster doses recommended due to waning immunity against new variants, including Delta. January 2022: Development and testing of variant-specific vaccine updates, especially targeting Omicron.

Figure 2

The SARS-CoV-2 variants of concern. Created with Biorender.

Figure 3

Chemical structures of fusion inhibitors that target S spike protein; Umifenovir, Camostat mesylate, and Nafamostat mesylate.

Figure 4

Chemical structures of protease inhibitors: Lopinavir, Ritonavir, Danoprevir, Saquinavir, and Ebselen.

Figure 5

Chemical structures of RNA-dependent RNA polymerase; Remedsivir, Favipiravir, Ribavirin, and Glidesivir.

Figure 6

Chemical structures of neuraminidase inhibitors, such as Oseltamivir, Zanamivir, and Peramivir.

Figure 7

Chemical structures of M2 channel protein target such as Admantane, Amantadine, and Rimantadine.

Figure 8

Chemical structures of some non-antiviral drugs, Chlorpromazine, Emetin, and Baricitnib.

Figure 9

The mechanism of SARS-CoV-2-neutralizing antibodies [204].

Figure 10

Chemical structures of Molnupiravir and Paxlovid.