Anthraquinolone and quinolizine derivatives as an alley of future treatment for COVID-19: an in silico machine learning hypothesis.

Coronavirus disease 2019 (Covid-19), caused by novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has come to the fore in Wuhan, China in December 2019 and has been spreading expeditiously all over the world due to its high transmissibility and pathogenicity. From the outbreak of COVID-19, many efforts are being made to find a way to fight this pandemic. More than 300 clinical trials are ongoing to investigate the potential therapeutic option for preventing/treating COVID-19. Considering the critical role of SARS-CoV-2 main protease (Mpro) in pathogenesis being primarily involved in polyprotein processing and virus maturation, it makes SARS-CoV-2 main protease (Mpro) as an attractive and promising antiviral target. Thus, in our study, we focused on SARS-CoV-2 main protease (Mpro), used machine learning algorithms and virtually screened small derivatives of anthraquinolone and quinolizine from PubChem that may act as potential inhibitor. Prioritisation of cavity atoms obtained through pharmacophore mapping and other physicochemical descriptors of the derivatives helped mapped important chemical features for ligand binding interaction and also for synergistic studies with molecular docking. Subsequently, these studies outcome were supported through simulation trajectories that further proved anthraquinolone and quinolizine derivatives as potential small molecules to be tested experimentally in treating COVID-19 patients.

Quantitative Insight into Immunopathology of SARS-CoV-2 Infection.

Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV-2), which initiated as an endemic from China, converted into a pandemic disease worldwide within a couple of months' time. This has led researchers from all over the world to come together to find and develop possible curative or preventive strategies, including vaccine development, drug repurposing, plasma therapy, drug discovery, and cytokine-based therapies. Herein, we are providing, a summarized overview of immunopathology of the SARS-CoV-2 along with various therapeutic strategies undertaken to COVID-19 with a vision for their possible outcome. High levels of proinflammatory cytokines such as interleukin (IL)-7, G-CSF, IP-10, TNF-α, monocyte chemoattractant protein-1 (MCP-1), and IL-2 in severe cases of COVID-19 have been observed. Immune responses play significant roles in the determination of SARS-CoV-2 pathogenesis. Thus, exploring the underlying mechanism of the immune system response to SARS-CoV-2 infection would help in the prediction of disease course and selection of intensive care and therapeutic strategy. As an effort toward developing possible therapeutics for COVID-19, we highlighted different types of vaccines, which are under clinical trials, and also discussed the impact of genome variability on efficacy of vaccine under development.

Evolutionary artificial intelligence based peptide discoveries for effective Covid-19 therapeutics.

An epidemic caused by COVID-19 in China turned into pandemic within a short duration affecting countries worldwide. Researchers and companies around the world are working on all the possible strategies to develop a curative or preventive strategy for the same, which includes vaccine development, drug repurposing, plasma therapy, and drug discovery based on Artificial intelligence. Therapeutic approaches based on Computational biology and Machine-learning algorithms are specially considered, with a view that these could provide a fast and accurate outcome in the present scenario. As an effort towards developing possible therapeutics for COVID-19, we have used machine-learning algorithms for the generation of alignment kernels from diverse viral sequences of Covid-19 reported from India, China, Italy and USA. Using these diverse sequences we have identified the conserved motifs and subsequently a peptide library was designed against them. Of these, 4 peptides have shown strong binding affinity against the main protease of SARS-CoV-2 (Mpro) and also maintained their stability and specificity under physiological conditions as observed through MD Simulations. Our data suggest that these evolutionary peptides against COVID-19 if found effective may provide cross-protection against diverse Covid-19 variants.