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Review
. 2021 Aug;129(2):104-129.
doi: 10.1111/bcpt.13600. Epub 2021 Jun 11.

An update on emerging therapeutics to combat COVID-19

Naveed Nazir Shah  1 , Showkat Ul Nabi  2 , Muzafar Ahmad Rather  3 , Qudratullah Kalwar  4 , Sofi Imtiyaz Ali  3 , Wajid Mohammad Sheikh  3 , Alveena Ganai  5 , Showkeen Muzamil Bashir  3
Affiliations
Review

An update on emerging therapeutics to combat COVID-19

Naveed Nazir Shah et al. Basic Clin Pharmacol Toxicol. 2021 Aug.

Abstract

Background: The COVID-19 pandemic has demanded effective therapeutic protocol from researchers and clinicians across the world. Currently, a large amount of primary data have been generated from several preclinical studies. At least 300 clinical trials are underway for drug repurposing against COVID-19; the clinician needs objective evidence-based medication to treat COVID-19.

Observations: Single-stranded RNA viral genome of SARS-CoV-2 encodes structural proteins (spike protein), non-structural enzymatic proteins (RNA-dependent RNA polymerase, helicase, papain-like protease, 3-chymotrypsin-like protease) and other accessory proteins. These four enzymatic proteins on spike protein are rate-limiting steps in viral replications and, therefore, an attractive target for drug development against SARS-CoV-2. In silico and in vitro studies have identified various potential epitomes as candidate sequences for vaccine development. These studies have also revealed potential targets for drug development and drug repurposing against COVID-19. Clinical trials utilizing antiviral drugs and other drugs have given inconclusive results regarding their clinical efficacy and side effects. The need for angiotensin-converting enzyme (ACE-2) inhibitors/angiotensin receptor blockers and corticosteroids has been recommended. Western countries have adopted telemedicine as an alternative to prevent transmission of infection in the population. Currently, no proven, evidence-based therapeutic regimen exists for COVID-19.

Conclusion: The COVID-19 pandemic has put tremendous pressure on researchers to evaluate and approve drugs effective against the disease. Well-controlled randomized trials should assess medicines that are not marketed with substantial evidence of safety and efficacy and more emphasis on time tested approaches for drug evaluation.

Keywords: COVID-19; coronavirus; drug repurposing; in vitro; in vivo and in silico.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Inhibition of viral spike protein binding with cellular receptors. Bromhexine hydrochloride and arbidol hydrochloride inhibit docking of ACE‐2 with S1 subunit hence inhibits viral phagocytosis (cellular internalization). Camostat inhibits TMPRSS2 cellular receptor, which is needed for priming of S protein and facilitation of docking between S1 and ACE‐2
FIGURE 2
FIGURE 2
Inhibition of viral receptor‐mediated viral phagocytosis. Hydroxychloroquine/Chloroquine Inhibits acidification of viral endosome hence inhibits viral phagocytosis (cellular internalization). Main SARS‐CoV‐2 protease inhibitors cause inhibition of viral protease and hence inhibit generation of viral proteins
FIGURE 3
FIGURE 3
Inhibition of RNA‐dependent RNA polymerase and viral assembly. Remdesivir inhibits RNA‐dependent RNA polymerase hence inhibits viral RNA synthesis, while HCQ/ Chloroquine causes alkalization of endosomes hence inhibits viral particle assembly
See this image and copyright information in PMC

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