Probing 3CL protease: Rationally designed chemical moieties for COVID ‐19

Mousmee Sharma, Parteek Prasher, Meenu Mehta, Flavia C. Zacconi, Yogendra Singh, Deepak N. Kapoor, Harish Dureja, Dinesh M. Pardhi, Murtaza M. Tambuwala, Gaurav Gupta, Dinesh K. Chellappan, Kamal Dua, Saurabh Satija

Research output: Contribution to journalArticle

Abstract

The outbreak of the COVID-19 pandemic has already pushed the worldwide morbidity and mortality rates to prodigious proportions, obligating deliberate efforts in identifying novel pharmacophores to manage the pathogenesis and, in addition, to target critical pathways that otherwise, sustain viral viability (Singh, Gupta, Satija, Negi, et al., 2020; Singh, Gupta, Satija, Pabreja et al., 2020). As per the latest WHO reports until June 2020, the COVID-19 pandemic claimed 0.3 million lives globally, with looming threat over 6.7 million confirmed cases (https://covid19.who.int/). Symptomized as severe acute respi- ratory syndrome (SARS), the COVID-19 infection, in addition to the Acute Respiratory Distress Syndrome (ARDS), manifests into moder- ate to acute pneumonia and aseptic shock (Gupta, Singh, Kumar Chellappan, & Dua, 2020; Xu et al., 2020). A multitude of regulatory protocols and lengthy clinical profile validations decelerated the de novo development of a novel drug molecule thereby creating an urgency to develop a swift chemotherapeutic regime to manage the present day health emergency. This encouraged a drug-repurposing approach to regulate and contain the disease eruption (Guy, DiPaola, Romanelli, & Dutch, 2020). However, the clinical limitations of several redeployed drugs apparently necessitated a paradigm shift in the strategy, which provided further impetus toward developing rationally designed pharmaceuticals. The prototypes for the development of such potentially active substances, that may inhibit the SARS-CoV-2 at the cellular level, then stemmed from the “lead” molecules that suc- cessfully countered MERS-CoV and SARS-CoV-1 (Anand, Ziebuhr, Wadhwani, Mesters, & Hilgenfeld, 2003).
Original languageEnglish
Number of pages8
JournalDrug Development Research
Early online date30 Jul 2020
DOIs
Publication statusE-pub ahead of print - 30 Jul 2020

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    Sharma, M., Prasher, P., Mehta, M., Zacconi, F. C., Singh, Y., Kapoor, D. N., Dureja, H., Pardhi, D. M., Tambuwala, M. M., Gupta, G., Chellappan, D. K., Dua, K., & Satija, S. (2020). Probing 3CL protease: Rationally designed chemical moieties for COVID ‐19. Drug Development Research. https://doi.org/10.1002/ddr.21724