SARS-CoV-2 has recently emerged as a pandemic that has caused more than 2.4 million deaths worldwide. Since the onset of infections, several full-length sequences of viral genome have been made available which have been used to gain insights into viral dynamics. We utilised a meta-data driven comparative analysis tool for sequences (Meta-CATS) algorithm to identify mutations in 829 SARS-CoV-2 genomes from around the world. The algorithm predicted sixty-one mutations among SARS-CoV-2 genomes. We observed that most of the mutations were concentrated around three protein coding genes viz nsp3 (non-structural protein 3), RdRp (RNA-directed RNA polymerase) and Nucleocapsid (N) proteins of SARS-CoV-2. We used various computational tools including normal mode analysis (NMA), C-α discrete molecular dynamics (DMD) and all-atom molecular dynamic simulations (MD) to study the effect of mutations on functionality, stability and flexibility of SARS-CoV-2 structural proteins including envelope (E), N and spike (S) proteins. PredictSNP predictor suggested that four mutations (L37H in E, R203K and P344S in N and D614G in S) out of seven were predicted to be neutral whilst the remaining ones (P13L, S197L and G204R in N) were predicted to be deleterious in nature thereby impacting protein functionality. NMA, C-α DMD and all-atom MD suggested some mutations to have stabilizing roles (P13L, S197L and R203K in N protein) where remaining ones were predicted to destabilize mutant protein. In summary, we identified significant mutations in SARS-CoV-2 genomes as well as used computational approaches to further characterize the possible effect of highly significant mutations on SARS-CoV-2 structural proteins. Communicated by Ramaswamy H. Sarma

Recently a novel coronavirus (SARS-CoV-2) emerged from Wuhan, China and has infected more than 571000 people leading to more than 26000 deaths. Since SARS-CoV-2 genome sequences show similarity with those of SARS, we sought to analyze all the available SARS-CoV-2 genomes based on the insights obtained from SARS genome specifically focusing on non-coding RNAs.Here, results are presented from the dual approach i.e identifying host encoded miRNAs that might regulate viral pathogenesis as well as identifying viral encoded miRNAs that might regulate host cell signaling pathways and aid in viral pathogenesis. Analysis utilizing first approach resulted in the identification of 10 host encoded miRNAs that could target the genome of both the viruses (SARS-CoV-2 and SARS reference genome). Interestingly our analysis revealed that there is significantly higher number of host miRNAs that could target SARS-CoV-2 genome as compared to the SARS reference genome. Results from second approach involving SARS-CoV-2 and SARS reference genome identified a set of virus encoded miRNAs which might regulate host signaling pathways. Our analysis further identified a similar "GA" rich motif in SARS-CoV-2 genome that was shown to play a vital role in lung pathogenesis during severe SARS infections. Hence, we successfully identified human and virus encoded miRNAs that might regulate pathogenesis of both these coronaviruses and the fact that more number of host miRNAs could target SARS-CoV-2 genomes possibly reveal as to why this virus follows mild pathogenesis in healthy individuals. We identified non-coding sequences in SARS-CoV-2 genomes that were earlier reported to contribute towards SARS pathology. The study provides insights into the overlapping sequences among these viruses for their effective inhibition as well as identifying new drug targets that could be used for development of new antivirals.

We performed a meta-analysis on SARS-CoV-2 genomes categorized by collection month and identified several significant mutations. Pearson correlation analysis of these significant mutations identified 16 comutations having absolute correlation coefficients of >0.4 and a frequency of >30% in the genomes used in this study.

Dengue virus can infect human megakaryocytes leading to decreased platelet biogenesis. In this article, we report a study of Dengue replication in human K562 cells undergoing PMA-induced differentiation into megakaryocytes. PMA-induced differentiation in these cells recapitulates steps of megakaryopoiesis including gene activation, expression of CD41/61 and CD61 platelet surface markers and accumulation of intracellular reactive oxygen species (ROS). Our results show differentiating megakaryocyte cells to support higher viral replication without any apparent increase in virus entry. Further, Dengue replication suppresses the accumulation of ROS in differentiating cells, probably by only augmenting the activity of the transcription factor NFE2L2 without influencing the expression of the coding gene. Interestingly pharmacological modulation of NFE2L2 activity showed a simultaneous but opposite effect on intracellular ROS and virus replication suggesting the former to have an inhibitory effect on the later. Also cells that differentiated while supporting intracellular virus replication showed reduced level of surface markers compared to uninfected differentiated cells.

Coronavirus‐induced disease‐19 (COVID‐19), caused by SARS‐CoV‐2, is still a major global health challenge. Human endogenous retroviruses (HERVs) represent retroviral elements that were integrated into the ancestral human genome. HERVs are important in embryonic development as well as in the manifestation of diseases, including cancer, inflammation, and viral infections. Here, we analyze the expression of several HERVs in SARS‐CoV‐2‐infected cells and observe increased activity of HERV‐E, HERV‐V, HERV‐FRD, HERV‐MER34, HERV‐W, and HERV‐K‐HML2. In contrast, the HERV‐R envelope is downregulated in cell‐based models and PBMCs of COVID‐19 patients. Overexpression of HERV‐R inhibits SARS‐CoV‐2 replication, suggesting its antiviral activity. Further analyses demonstrate the role of the extracellular signal‐regulated kinase (ERK) in regulating HERV‐R antiviral activity. Lastly, our data indicate that the crosstalk between ERK and p38 MAPK controls the synthesis of the HERV‐R envelope protein, which in turn modulates SARS‐CoV‐2 replication. These findings suggest the role of the HERV‐R envelope as a prosurvival host factor against SARS‐CoV‐2 and illustrate a possible advantage of integration and evolutionary maintenance of retroviral elements in the human genome.