Inhibiting Property of Phytoconstituents of ‘Aconitum Heterophyllum’ Against Omicron Variant of SARS-CoV-2: Molecular Docking, Molecular Dynamic and MM-GBSA approach (preprint)

Omicron’s traces have been found significantly faster than the Delta variant. Persons who already have been vaccinated are also affected by this variant. This shows that vaccines taken to combat COVID-19 are less effective in preventing the Omicron’s transmission. Thus, the identification of effective candidates to fight against Omicron has been the top priority in pharmaceutics. The present study deals with the investigation of the antiviral activities of the phytocompounds of Aconitum heterophyllum against the Omicron variant. The systematic in-silico study done in the paper reveals the good binding of Isoatisine with spike glycoprotein of Omicron. Isoatisine molecule follows most of the pharmacokinetic properties that make it a better drug-like molecule. The computed global reactivity parameters fairly justified the high reactivity of the Isoatisine molecule. This study aims to discover the novel antiviral activity of Isoatisine to counter the Omicron protein. The results of this study can also be considered for experimental validation and clinical trials.

In-Silico Investigation of Inhibiting Property of Phytoconstituents of Medicinal Herb ‘Aconitum Heterophyllum’ Against Omicron Variant of SARS-CoV-2 (preprint)

Omicron’s traces have been found significantly faster than the Delta variant. Persons who already have been vaccinated are also affected by this variant. This shows that vaccines taken to combat COVID-19 are less effective in preventing the Omicron’s transmission. Thus, the identification of effective candidates to fight against Omicron has been the top priority in pharmaceutics. The present study deals with the investigation of the antiviral activities of the phytocompounds of Aconitum heterophyllum against the Omicron variant. The systematic in-silico study done in the paper reveals the good binding of Isoatisine with spike glycoprotein of Omicron. Isoatisine molecule follows most of the pharmacokinetic properties that make it a better drug-like molecule. The computed global reactivity parameters fairly justified the high reactivity of the Isoatisine molecule. This study aims to discover the novel antiviral activity of Isoatisine to counter the Omicron protein. The results of this study can also be considered for experimental validation and clinical trials.

Blood transcriptomes of SARS-CoV-2 infected kidney transplant recipients demonstrate immune insufficiency (preprint)

BackgroundKidney transplant recipients (KTRs) with COVID-19 have poor outcomes compared to non-KTRs. To provide insight into management of immunosuppression during acute illness, we studied immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort.{square} MethodsClinical data were collected by chart review. PAXgene blood RNA was poly-A selected and RNA sequencing was performed to evaluate transcriptome changes. ResultsA total of 64 cases of COVID-19 in KTRs were enrolled, including 31 acute cases (< 4 weeks from diagnosis) and 33 post-acute cases (>4 weeks). In the blood transcriptome of acute cases, we identified differentially expressed genes (DEGs) in positive or negative association COVID-19 severity scores. Functional enrichment analyses showed upregulation of neutrophil and innate immune pathways, but downregulation of T-cell and adaptive immune-activation pathways proportional to severity score. This finding was independent of lymphocyte count and despite reduction in immunosuppression (IS) in most KTRs. Comparison with post-acute cases showed "normalization" of these enriched pathways after >4 weeks, suggesting recovery of adaptive immune system activation despite reinstitution of IS. The latter analysis was adjusted for COVID-19 severity score and lymphocyte count. DEGs associated with worsening disease severity in a non-KTR cohort with COVID-19 (GSE152418) showed significant overlap with KTRs in these identified enriched pathways. ConclusionBlood transcriptome of KTRs affected by COVID-19 shows decrease in T-cell and adaptive immune activation pathways during acute disease that associate with severity despite IS reduction and show recovery after acute illness. Significance statementKidney transplant recipients (KTRs) are reported to have worse outcomes with COVID-19, and empiric reduction of maintenance immunosuppression is pursued. Surprisingly, reported rates of acute rejection have been low despite reduced immunosuppression. We evaluated the peripheral blood transcriptome of 64 KTRs either during or after acute COVID-19. We identified transcriptomic signatures consistent with suppression of adaptive T-cell responses which significantly associated with disease severity and showed evidence of recovery after acute disease, even after adjustment for lymphocyte number. Our transcriptomic findings of immune-insufficiency during acute COVID-19 provide an explanation for the low rates of acute rejection in KTRs despite reduced immunosuppression. Our data support the approach of temporarily reducing T -cell-directed immunosuppression in KTRs with acute COVID-19.

A Computational Study of Ivermectin and Doxycycline Combination Drug Against SARS-CoV-2 Infection (preprint)

In the present study, we have described how by using molecular docking and molecular dynamics (MD) simulation studies the combination drug of ivermectin and doxycycline can be used as a potential inhibitor for Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) virus. In lieu of unavailability of specific cure of coronavirus disease of 2019 (COVID-19) till now various possibilities for individual and combination drugs have been explored by the medical practitioners/scientists for the remedial purpose of CoV-2 infections. 3C-like protease (3CLpro) is the main protease of SARS-CoV-2 virus which plays an essential role in mediating viral replication in the human body. 3CLpro protein can serve as an attractive drug target. In this work, we have studied drug: 3CLpro interactions by in-silico molecular docking and MD simulation approaches. Common and easily available antiviral drugs ivermectin, doxycycline and their combination can regulate 3CLpro protein's function due to its easy inhibition.

Ivermectin and Doxycycline Combination as a Promising Drug Candidate Against SARS-CoV-2 Infection: A Computational Study (preprint)

In the present study, we have described how by using molecular docking and molecular dynamic (MD) simulation studies the combination drug of ivermectin and doxycycline can be used as a potential inhibitor for SARS-CoV-2 virus. In lieu of unavailability of specific cure of COVID-19 till now various possibilities for individual and combination drugs have been explored by the medical practitioners/scientists for the remedial purpose of CoV-2 infections. $3CL^{pro}$ is the main protease of SARS-CoV-2 virus which plays an essential role in mediating viral replication in the human body. $3CL^{pro}$ protein can serve as an attractive drug target. In this work, we have studied drug: $3CL^{pro}$ interactions by in silico molecular docking and MD simulation approaches. Common and easily available antiviral drugs ivermectin, doxycycline and their combination have been proved their valid candidature to be used as potential drug candidates against SARS-CoV-2 infections.