Glycocin F for COVID-19

The emergence and rapid evolution of human pathogenic viruses, combined with the difficulties in developing effective vaccines, underline the need to develop innovative broad-spectrum antiviral therapeutic agents. The present study aims to determine the in silico antiviral potential of six bacterial antimicrobial peptides (AMPs), two phytochemicals (silvestrol, andrographolide), and two bacterial secondary metabolites (lyngbyabellin A, hapalindole H) against dengue virus, Zika virus, Ebola virus, the major variants of SARS-CoV-2 and monkeypox virus. The comparison of docking scores obtained with natural biomolecules was performed with specific neutralizing antibodies (positive controls for ClusPro) and antiviral drugs (negative controls for Autodock Vina). Glycocin F was the only natural biomolecule tested to show high binding energies to all viral surface proteins and the corresponding viral cell receptors. Lactococcin G and plantaricin ASM1 also achieved high docking scores with all viral surface proteins and most corresponding cell surface receptors. Silvestrol, andrographolide, hapalindole H, and lyngbyabellin A showed variable docking scores depending on the viral surface proteins and cell receptors tested. Three glycocin F mutants with amino acid modifications showed an increase in their docking energy to the spike proteins of SARS-CoV-2 B.1.617.2 Indian variant, and of the SARS-CoV-2 P.1 Japan/Brazil variant, and the dengue DENV envelope protein. All mutant AMPs indicated a frequent occurrence of valine and proline amino acid rotamers. AMPs and glycocin F in particular are the most promising biomolecules for the development of broad-spectrum antiviral treatments targeting the attachment and entry of viruses into their target cell.

Abstract: Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the recent pandemic and worldwide outbreak of respiratory disease. Since there are no known specific drugs for fighting this virus and the process for new drug development is lengthy, scientists have been trying to develop drugs against this viral infection. The potent antiviral activity of natural products has been confirmed in several previous studies. Viral and host proteins contributing to COVID-19 infections can be targeted by natural compounds derived from plants, marine organisms, and microorganisms. The most important of these compounds are polyphenols (e.g., anthraquinone polyphenol, hinokinin, curcumin, and epigallocatechin gallate), alkaloids (e.g., isoquinoline, 10- hydroxyusambarensine, anisotine, and adhatodine), and terpenoids (salvinorin A, thymoquinone, bilobalide, ginkgolide A, and celastrol) from plants, sulphated polysaccharides (carrageenans, chondroitin sulfate C, and fucoidan) from marine organisms, and glycocin F and lactococcin G phycocyanin, and lipopeptide from microorganisms. This study reviews these compounds and their mechanism of action for treating COVID-19 infection and guides researchers in developing effective and safe therapeutic agents against this disease from naturally derived compounds.