ISSN: 2471-9315
Renu Wadhwa1, Jaspreet Kaur Dhanjal1, Vipul Kumar2, Sunil C Kaul1*, Durai Sundar2*
A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-coronavirus 2; SARS-CoV-2)
emerged in December 2019 in Wuhan, China, and caused fatal Coronavirus disease 2019 (COVID-19). It became
an international pandemic, disrupted all aspects of normal life and called global health emergency. High infected
numbers and deaths world-wide have evoked urgent initiation of new line of drug and vaccine development on one
hand, and repurposing of the existing drugs on the other. Because of the immunity enhancing properties of several
kinds of traditional home medicine, they have been recommended for the prevention and treatment of COVID-19.
Ashwagandha, an Ayurvedic herb that enjoys 5000 years of history was explored for its potential for antiCOVID-19
activity using bioinformatics and experimental technologies. Active with anolides of Ashwagandha (Withaferin-A;
Wi-A and Withanone; Wi-N) were tested for their binding to a highly conserved protein (Mpro, an essential protein
for virus replication and survival) of SARS-CoV-2. Wi-N, but not Wi-A, showed strong binding to Mpro with the
binding energy equivalent to a known Mpro inhibitor (N3) predicting that Wi-N may serve as natural drug for
COVID-19. We also examined potential of Wi-A and Wi-N to bind to a cell membrane protein (TPMRSS2) that
acts as a gate for entry of virus to the host cell. We found that although both Wi-A and Wi-N could bind and stably
interact with TMPRSS2, Wi-N showed stronger interactions. Furthermore, human cells treated with Wi-N showed
low level of expression of TMPRSS2 predicting three-way action of Wi-N to deal with SARS-CoV-2 (blocking its
entry to the host cells by interaction with TMPRSS2, downregulation of TMPRSS2 expression and diminishing the
viral survival through inhibition of viral Mpro protein).