Computational Investigation Of Cordycepin As A Potential SARS-Cov-2 Inhibitor: A Step Toward Efficient Antiviral Therapy

Abstract

The outbreak of COVID-19 pandemic causing virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) underscores the urgent need for affordable and effective antiviral agents. Natural nucleoside analogues such as cordycepin (3′-deoxyadenosine) have emerged as promising candidates due to their structural similarity to adenosine and broad biological activities. In this study, an integrated in-silico approach was employed to evaluate the therapeutic potential of cordycepin against SARS-CoV-2. Molecular docking demonstrated stable binding of cordycepin within the catalytic site of the viral main protease (Mpro), a key enzyme in viral replication, with a predicted binding affinity of -6.3 kcal mol⁻¹, indicating a moderate yet biologically relevant interaction consistent with competitive inhibition. Complementary ADMET and drug-likeness analyses revealed favorable physicochemical and pharmacokinetic properties, including optimal molecular weight, balanced hydrogen-bonding profile, high gastrointestinal absorption, absence of P-glycoprotein substrate liability, and non-inhibitory behavior toward major cytochrome P450 isoforms. Cordycepin complied with multiple drug-likeness filters, lacked structural alerts for toxicity, and exhibited a moderate bioavailability score with reasonable synthetic accessibility. Collectively, these computational findings support cordycepin as a promising natural lead compound for anti-SARS-CoV-2 drug development. Nevertheless, experimental validation through enzymatic inhibition assays and in-vitro studies is warranted to confirm its efficacy and safety, thereby establishing a rational basis for its advancement into in-vivo and preclinical development.