The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak in December 2019 has caused a global pandemic. The rapid mutation rate in the virus has created alarming situations worldwide and is being attributed to the false negativity in RT-PCR tests. It has also increased the chances of reinfection and immune escape. Recently various lineages namely, B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.617.3 have caused rapid infection around the globe. To understand the biophysical perspective, we have performed molecular dynamic simulations of four different spikes (receptor binding domain)-hACE2 complexes, namely wildtype (WT), Alpha variant (N501Y spike mutant), Kappa (L452R, E484Q) and Delta (L452R, T478K), and compared their dynamics, binding energy and molecular interactions. Our results show that mutation has caused significant increase in the binding energy between the spike and hACE2 in Alpha and Kappa variants. In the case of Kappa and Delta variants, the mutations at L452R, T478K and E484Q increased the stability and intra-chain interactions in the spike protein, which may change the interaction ability of neutralizing antibodies to these spike variants. Further, we found that the Alpha variant had increased hydrogen interaction with Lys353 of hACE2 and more binding affinity in comparison to WT. The current study provides the biophysical basis for understanding the molecular mechanism and rationale behind the increase in the transmissivity and infectivity of the mutants compared to wild-type SARS-CoV-2.

Reliable, fast, and affordable diagnosis for tuberculosis (TB) remains a challenge to reduce disease incidence in resource-poor countries. Tests based on nucleotide sequences that are signature to Mycobacterium tuberculosis have the potential to make a positive impact on case detection rates, which can eventually help control TB. Using extensive comparative bioinformatics approach, we mined the genome for M. tuberculosis-specific genes and identified four genes so-called signature sequence (SS). With <25% homology with other known genes/proteins of mycobacterial/nonmycobacterial origin in various databases, these SS genes are ideal targets for species-specific identification. Sputum from suspected patients was liquefied using novel complete liquefying reagent, and DNA was isolated. Samples from patients (n = 417), reporting to TB clinics at two different hospitals, which met our inclusion criteria, were collected for this study. A small number (n = 143) was used for initial standardization, and the remaining patient samples (n = 274) were evaluated by SS and compared with smear microscopy, GeneXpert, culture, and clinical outcome. An overwhelming sensitivity of 97.0%, significantly higher than GeneXpert (95.0%), was seen. SS could pick all smear-negative, but culture-positive samples, along with other culture-negative samples; some of the latter were declared clinically positive. Our results yielded superior sensitivity and specificity through conventional PCR.

• MycoTRAP-DB, a database of mutations and their impact on normal functionality of protein in M.tb genes. • Several secondary mutations were identified with significant impact on protein structure and function. • Comprehensive information gives insight for screening of suspected hotspots in advance to combat drug resistant TB.

The Severe Acute syndrome corona Virus 2 (SARS-CoV-2) outbreak in December 2019 has caused a global pandemic. The rapid mutation rate in the virus has caused alarming situations worldwide and is being attributed to the false negativity in RT-PCR tests, which also might lead to inefficacy of the available drugs. It has also increased the chances of reinfection and immune escape. We have performed Molecular Dynamic simulations of three different Spike-ACE2 complexes, namely Wildtype (WT), B.1.1.7 variant (N501Y Spike mutant) and B.1.617 variant (L452R, E484Q Spike mutant) and compared their dynamics, binding energy and molecular interactions. Our result shows that mutation has caused the increase in the binding energy between the Spike and hACE2. In the case of B.1.617 variant, the mutations at L452R and E484Q increased the stability and intra-chain interactions in the Spike protein, which may change the interaction ability of human antibodies to this Spike variant. Further, we found that the B.1.1.7 variant had increased hydrogen interaction with LYS353 of hACE2 and more binding affinity in comparison to WT. The current study provides the biophysical basis for understanding the molecular mechanism and rationale behind the increase in the transmissivity and infectivity of the mutants compared to wild-type SARS-CoV-2.