Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach.

COVID-19 is an infectious and pathogenic viral disease caused by SARS-CoV-2 that leads to septic shock, coagulation dysfunction, and acute respiratory distress syndrome. The spreading rate of SARS-CoV-2 is higher than MERS-CoV and SARS-CoV. The receptor-binding domain (RBD) of the Spike-protein (S-protein) interacts with the human cells through the host angiotensin-converting enzyme 2 (ACE2) receptor. However, the molecular mechanism of pathological mutations of S-protein is still unclear. In this perspective, we investigated the impact of mutations in the S-protein and their interaction with the ACE2 receptor for SAR-CoV-2 viral infection. We examined the stability of pathological nonsynonymous mutations in the S-protein, and the binding behavior of the ACE2 receptor with the S-protein upon nonsynonymous mutations using the molecular docking and MM_GBSA approaches. Using the extensive bioinformatics pipeline, we screened the destabilizing (L8V, L8W, L18F, Y145H, M153T, F157S, G476S, L611F, A879S, C1247F, and C1254F) and stabilizing (H49Y, S50L, N501Y, D614G, A845V, and P1143L) nonsynonymous mutations in the S-protein. The docking and binding free energy (ddG) scores revealed that the stabilizing nonsynonymous mutations show increased interaction between the S-protein and the ACE2 receptor compared to native and destabilizing S-proteins and that they may have been responsible for the virulent high level. Further, the molecular dynamics simulation (MDS) approach reveals the structural transition of mutants (N501Y and D614G) S-protein. These insights might help researchers to understand the pathological mechanisms of the S-protein and provide clues regarding mutations in viral infection and disease propagation. Further, it helps researchers to develop an efficient treatment approach against this SARS-CoV-2 pandemic.

Investigation of the antimicrobial activity and hematological pattern of nano-chitosan and its nano-copper composite.

Novel synthesized Chitosan-Copper oxide nanocomposite (Cs-CuO) was prepared using pomegranate peels extract as green precipitating agents to improve the biological activity of Cs-NP's, which was synthesized through the ionic gelation method. The characterization of biogenic nanoparticles Cs-NP's and Cs-CuO-NP's was investigated structurally, morphologically to determine all the significant characters of those nanoparticles. Antimicrobial activity was tested for both Cs-NP's and Cs-CuO-NP's via minimum inhibition concentration and zone analysis against fungus, gram-positive and gram-negative. The antimicrobial test results showed high sensitivity of Cs-CuO-NP's to all microorganisms tested in a concentration less than 20,000 mg/L, while the sensitivity of Cs-NP's against all microorganisms under the test started from a concentration of 20,000-40,000 mg/L except for the C. albicans species. The hematological activity was also tested via measuring the RBCs, platelet count, and clotting time against healthy, diabetic, and hypercholesteremia blood samples. The measurement showed a decrease in RBCs and platelet count by adding Cs-NP's or Cs-CuO-NP's to the three blood samples. Cs-NP's success in decreasing the clotting time for healthy and diabetic blood acting as a procoagulant agent while adding biogenic CuO-NP's to Cs-NP's increased clotting time considering as an anti-coagulant agent for hypercholesteremia blood samples.