An overview of key potential therapeutic strategies for combat in the COVID-19 battle

Abstract

The sudden ravaging outbreak of a novel coronavirus, or SARS-CoV-2, in terms of virulence, severity, and casualties has already overtaken previous versions of coronaviruses, like SARS CoV and MERS CoV. Originating from its epicenter in Wuhan, China, this mutated version of the influenza virus with its associated pandemic effects has engulfed the whole world with awful speed. In the midst of this bewildering situation, medical and scientific communities are on their toes to produce the potential vaccine-mediated eradication of this virus. Though the chances are really high, to date no such panacea has been reported. The time requirements for the onerous procedures of human trials for the successful clinical translation of any vaccine or potential therapeutics are also a major concern. In order to build some resistance against this massive pandemic, the repurposing of some earlier antiviral drugs has been done, along with the refurbishment of some immune-responsive alternative avenues, like monoclonal antibody mediated neutralization, interferon treatment, and plasma therapy. New drugs developed from the RBD domain of the virus spike protein and drugs targeting viral proteases are also undergoing further research and have shown potential from preliminary results. The sole purpose of this review article is to provide a brief collective overview of the recent status of therapeutics advances and approaches, and their current state of implementation for the management of COVID-19.

Fig. 1. The structure of SARS-CoV-2.

Fig. 2. (A and B) Small-molecule-based drug structures.

Fig. 3. The viral life cycle and potential therapeutic targets.

Fig. 4. Preliminary blind docking data revealed the interacting stretch of amino acids of the ACE2 receptor (red) with the viral spike RBD (cyan): the ‘Hotspot’ zone.

Fig. 5. (A) The mechanism of interaction between ACE2 and the S subunits of SARS-CoV-2 to facilitate the entry of the virus into the cells. (B) The inhibition of SARS CoV-2 by developing potent peptide-based inhibitors targeting the HR1–HR2 interaction at the S2 protein of the coronavirus.

Fig. 6. Repurposed small-molecule drugs.

Fig. 7. The monoclonal antibody mediated neutralization of the RBD of the spike protein of the COVID-19 virus.

Fig. 8. A schematic diagram representing the workflow for convalescent plasma therapy.

Fig. 9. A schematic illustrated mechanism of different types of potential vaccine for SARS-CoV-2 in the context of developing immunity in the host.