In silico Design of a Vaccine Candidate for SAR S-CoV-2 Based on Multiple T-cell and B-cell Epitopes.

Coronaviruses (2019-nCoV) are large single-stranded RNA viruses that usually cause respiratory infections with a crude lethality ratio of 3.8% and high levels of transmissibility. There is yet no applicable clinical evaluation to assess the efficacy of various therapeutic agents that have been suggested as investigational drugs against the viruses despite their respective supposed hypothetical claims due to their antiviral potentials. Moreover, the development of a safe and effective vaccine has been suggested as an intervention to control the 2019-nCoV pandemic. However, a major concern in the development of a 2019-nCoV vaccine is the possibility of stimulating a corresponding immune response without enhancing the induction of the disease and associated side effects. The present investigation was carried out by predicting the antigenicity of the primary sequences of 2019-nCoV structural proteins and identification of B-cell and T-cell epitopes through the Bepipred and PEPVAC servers, respectively. The peptides of the vaccine construct include the selected epitopes based on the VaxiJen score with a threshold of 1.0 and ß-defensinas an adjuvant. The putative binding of the vaccine constructs to intracellular toll-like receptors (TLRs) was assessed through molecular docking analysis and molecular dynamics simulations. The selected epitopes for the final vaccine construct are DPNFKD, SPLSLN, and LELQDHNE as B-cell epitopes and EPKLGSLVV, NFKDQVILL, and SSRSSSRSR as T-cell epitopes. The molecular docking analysis showed the vaccine construct could have favorable interactions with TLRs as indicated by the negative values of the computed binding energies. The constructed immunogen based on the immune informatics study could be employed in the strategy to develop potential vaccine candidates against 2019-nCoV.

Molecular Docking and ADMET Prediction of Natural Compounds towards SARS Spike Glycoprotein-Human Angiotensin-Converting Enzyme 2 and SARS-CoV-2 Main Protease.

More than a decade ago, a novel coronavirus that infects humans, bats, and certain other mammals termed severe acute respiratory syndrome coronavirus (SARS-CoV) caused an epidemic with ~ 10% case fatality, creating global panic and economic damage. Recently, another strain of the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused an infectious disease (COVID-19) in humans which was detected for the first time in Wuhan, China. Presently, there is no specific therapy available for the treatment of COVID-19. However, social distancing, patient isolation, and supportive medical care make up the current management for this current infectious disease pandemic. The present in silico study evaluated the binding affinities of some natural products (resveratrol, xylopic acid, ellagic acid, kaempferol, and quercetin) to human angiotensin-converting enzyme 2 and coronavirus (SARS-CoV-2) main protease compared to chloroquine, an inhibitor known to prevent cellular entry and replication of the coronavirus. The respective binding energies of the selected natural compounds and chloroquine towards the proteins were computed using PyRx virtual screening tool. The pharmacodynamic and pharmacokinetic attributes of the selected compounds were predicted using admetSAR. Molecular docking analysis showed that the natural compounds had better scores towards the selected protein compared to chloroquine with polar amino acid residues present at the binding sites. The predicted ADMET properties revealed the lower acute oral toxicity of the natural products compared to chloroquine. The study provides evidence suggesting that the relatively less toxic compounds from the natural sources could be repositioned as anti-viral agents to prevent the entry and replication of SARS-CoV-2.

Theoretical studies of plant-based peptides targeting human angiotensin converting enzyme-related carboxypeptidase

Background The vulnerability of the lungs, intestine, heart and kidney to SARS-CoV-2 invasion is dependent on the high expression of angiotensin converting enzyme-related carboxypeptidase (ACE2) on the outer surface of the cells in these organs. This clear mode of interaction between SARS-CoV-2 spike proteins and ACE2 emphasizes the importance of ACE2 receptors in the spread of coronaviruses. This study investigated the binding potentials of some selected plant-based peptides (circulin A, kalata B1, Varv peptide E, palicourein, Vhl-1, griffithsin, cycloviolacin VY1) to ACE2 as a predictive approach in preventing SARS-CoV-2 invasion. Methods The peptides were retrieved from the antimicrobial peptide database and their respective physicochemical properties were predicted using ProtParam Tool. The binding mode and the binding free energies were computed through HawkDock servers while the structural flexibility and stability of the ACE2-peptide complexes were evaluated via the CABS-flex 2.0 server. Results It was observed that the binding scores for the peptides towards ACE2 showed good binding affinities with griffithsin having the best binding score through the Hawkdock rank while kalata B1 had the lowest binding score. The Molecular Mechanics/Generalized Born Surface Area analysis showed that the binding free energy ranges-39.99 and-3.96 kcal/mol with Vhl-1 having the highest free energy and palicourein having the least free energy. Conclusions The results of the study suggest that the selected plant-based peptides especially kalata B1, vhl-1, and cycloviolacin VY1 could be promising modulators of ACE2 and prevent the binding of the S1 domain of the SARS-CoV-2 S protein and consequent cellular entry of SARS-CoV-2.