AntiCoV-DB: A novel database resource of Anti COVID- 19, Anti CoronaVirus, Natural products and peptides (preprint)

SARS-CoV-2 is one of the most common pathogens. SARS-CoV-2 has shown 80% genome identity with other Corona viruses. Due to the high rate of infection reported in the COVID-19 pandemic, in recent months, a lot of studies have been performed on the introduction of antiviral drugs. Secondary metabolites as alkaloids, essential oils, flavonoids, polyphenols and other natural compounds have shown promise as antiviral agents against several pathogenic viruses including SARS-CoV-2. The antimicrobial peptides display narrow-or broad spectrum activity against microbes including COVID-19 causative agent. The gathering of such data related to these molecules in one central database resource would therefore be of great benefit to the exploitation of these anti-coronavirus peptides and anti-COVID-19 secondary metabolites in the present context of increasing contagiousness in humans and its spread across the globe. The database AntiCov-DB has been developed to facilitate access to important information on 294 secondary metabolites with 90 alkaloids, 18 essential oils, 88 flavonoids, 15 polyphenols, 93 other natural compounds, 34 peptides anti-COVID-19 and 104 antimicrobial sequences of peptides reported to act as anti-CoronaVirus. The database permits a quick and easy search on the one hand of secondary metabolites based on their target molecules of COVID-19 and general data and on the other hand of antiviral peptides based on their activity as well as their general, physicochemical properties and literature. AntiCoV-DB is hosted on the web server at the Institut Pasteur de Tunis, Tunisia (IPT) and is freely available through this link: http://tesla.pasteur.tn/DBs/AntiCoV_DB/index.php

SARS-CoV-2 spike protein unlikely to bind to integrins via the Arg-Gly-Asp (RGD) motif of the Receptor Binding Domain: evidence from structural analysis and microscale accelerated molecular dynamics (preprint)

The Receptor Binding Domain (RBD) of SARS-CoV-2 virus harbors a sequence of Arg-Gly-Asp tripeptide named RGD motif, which has also been identified in extracellular matrix proteins that bind integrins as well as other disintegrins and viruses. Accordingly, integrins have been proposed as host receptors for SARS-CoV-2. The hypothesis was supported by sequence and structural analysis. However, given that the microenvironment of the RGD motif imposes structural hindrance to the protein-protein association, the validity of this hypothesis is still uncertain. Here, we used normal mode analysis, accelerated molecular dynamics microscale simulation, and protein-protein docking to investigate the putative role of RGD motif of SARS-CoV-2 RBD for interacting with integrins. We found, by molecular dynamics, that neither RGD motif nore its microenvironment show any significant conformational shift in the RBD structure. Highly populated clusters were used to run a protein-protein docking against three RGD-binding integrin types, showing no capability of the RBD domain to interact with the RGD binding site. Moreover, the free energy landscape revealed that the RGD conformation within RBD could not acquire an optimal geometry to allow the interaction with integrins. Our results highlighted different structural features of the RGD motif that may prevent its involvement in the interaction with integrins. We, therefore, suggest, in the case where integrins are confirmed to be the direct host receptors for SARS-CoV-2, a possible involvement of other residues to stabilize the interaction.