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.

In silico comparative study of SARS-CoV-2 proteins and antigenic proteins in BCG, OPV, MMR and other vaccines: evidence of a possible putative protective effect (preprint)

Background: Coronavirus Disease 2019 (COVID-19) is a viral pandemic disease that may induce severe pneumonia in humans. In this paper, we investigated the putative implication of 12 vaccines, including BCG, OPV and MMR in the protection against COVID-19. Sequences of the main antigenic proteins in the investigated vaccines and SARS-CoV-2 proteins were compared to identify similar patterns. The immunogenic effect of identified segments was, then, assessed using a combination of structural and antigenicity prediction tools.Results: A total of 14 highly similar segments were identified in the investigated vaccines. Structural and antigenicity prediction analysis showed that, among the identified patterns, three segments in Hepatitis B, Tetanus, and Measles proteins presented antigenic properties that can induce putative protective effect against COVID-19. Conclusions: Our results suggest a possible protective effect of HBV, Tetanus and Measles vaccines against COVID-19, which may explain the variation of the disease severity among regions.

G6PD variant distribution in sub-Saharan Africa and potential risks ofusing chloroquine/hydroxychloroquine based treatments forCOVID-19 (preprint)

Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole-genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identified nine variants, of which four are potentially deleterious to G6PD function, and one (rs1050828) that is known to cause G6PD deficiency. We supplemented data for the rs1050828 variant with genotype array data from over 11,000 Africans. Although this variant is common in Africans overall, large allele frequency differences exist between sub-populations. African sub-populations in the same country can show significant differences in allele frequency (e.g. 16.0% in Tsonga vs 0.8% in Xhosa, both in South Africa, {rho}=2.4x10-3). The high prevalence of variants in the G6PD gene found in this analysis suggests that it may be a significant interaction factor in clinical trials of chloroquine and hydrochloroquine for treatment of COVID-19 in Africans.

In silico study of the spike protein from SARS-CoV-2 interaction with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism (preprint)

The spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.