In silico study identifies peptide inhibitors that negate the effect of non-synonymous mutations in major drug targets of SARS-CoV-2 variants.

Since its advent in December 2019, SARS-CoV-2 has diverged into multiple variants with differing levels of virulence owing to the accumulation of mutations in its genome. The structural changes induced by non-synonymous mutations in major drug targets of the virus are known to alter the binding of potential antagonistic inhibitors. Here, we analyzed the effects of non-synonymous mutations in major targets of SARS-CoV-2 in response to potential peptide inhibitors. We screened 12 peptides reported to have anti-viral properties against RBD and 5 peptides against Mpro of SARS-CoV-2 variants using molecular docking and simulation approaches. The mutational landscape of RBD among SARS-CoV-2 variants had 21 non-synonymous mutations across 18 distinct sites. Among these, 14 mutations were present in the RBM region directly interacting with the hACE2 receptor. However, Only 3 non-synonymous mutations were observed in Mpro. We found that LCB1 - a de novo-synthesized peptide has the highest binding affinity to RBD despite non-synonymous mutations in variants and engages key residues of RBD-hACE2 interaction such as K417, E484, N487, and N501. Similarly, an antimicrobial peptide; 2JOS, was identified against Mpro with high binding affinity as it interacts with key residues in dimerization sites such as E166 and F140 crucial for viral replication. MD simulations affirm the stability of RBD-LCB1 and Mpro-2JOS complexes with an average RMSD of 1.902 and 2.476 respectively. We ascertain that LCB1 and 2JOS peptides are promising inhibitors to combat emerging variants of SARS-CoV-2 and thus warrant further investigations using in-vitro and in-vivo analysis.Communicated by Ramaswamy H. Sarma.

Effect of Dietary L-Threonine and Toxin Binder on Performance, Blood Parameters, and Immune Response of Broilers Exposed to Aflatoxin B1.

To evaluate the effect of L-Threonine (L-Thr) and Mycofix® Plus (MP) on aflatoxicosis, an experiment with a 3-way ANOVA model was carried out with 8 replicates and 640 birds. Treatments included two levels of L-Thr (100% and 125% of the requirements, Cobb 500, Cobb-Vantress), Aflatoxin B1 (AFB1) (0, 500 ppb), and MP (0, 1 g/kg). As the main effects showed, AFB1 decreased breast meat yield and carcass percentage (p < 0.001), serum urea, antibody titer against infectious bronchitis virus (IBV), and bone density (p < 0.05), while it increased the plasma concentrations of glucose and alkaline phosphatase (ALP) (p < 0.05). Mycofix Plus improved the grower feed intake (FI), tibia fresh weight, and body weight (BW) to bone weight (p < 0.05). L-Threonine increased the grower FI, breast meat yield, serum aspartate transaminase (AST), and glutathione peroxidase (GPX) (p < 0.05). There were positive interactions with breast meat yield, cholesterol, lactate dehydrogenase (LDH), and IBV titer. Of the treatments used, the combination of L-Thr and MP without AFB1 improved breast meat and carcass percentage. L-Threonine and MP significantly improved IBV titer in birds challenged with AFB1 (p < 0.001). In conclusion, L-Thr and MP were beneficial to improve immunity.