Comparative analysis of SARS-CoV-2 envelope viroporin mutations from COVID-19 deceased and surviving patients revealed implications on its ion-channel activities and correlation with patient mortality.

One major obstacle in designing a successful therapeutic regimen to combat COVID-19 pandemic is the frequent occurrence of mutations in the SARS-CoV-2 resulting in patient to patient variations. Out of the four structural proteins of SARS-CoV-2 namely, spike, envelope, nucleocapsid and membrane, envelope protein governs the virus pathogenicity and induction of acute-respiratory-distress-syndrome which is the major cause of death in COVID-19 patients. These effects are facilitated by the viroporin (ion-channel) like activities of the envelope protein. Our current work reports metagenomic analysis of envelope protein at the amino acid sequence level through mining all the available SARS-CoV-2 genomes from the GISAID and coronapp servers. We found majority of mutations in envelope protein were localized at or near PDZ binding motif. Our analysis also demonstrates that the acquired mutations might have important implications on its structure and ion-channel activity. A statistical correlation between specific mutations (e.g. F4F, R69I, P71L, L73F) with patient mortalities were also observed, based on the patient data available for 18,691 SARS-CoV-2-genomes in the GISAID database till 30 April 2021. Albeit, whether these mutations exist as the cause or the effect of co-infections and/or co-morbid disorders within COVID-19 patients is still unclear. Moreover, most of the current vaccine and therapeutic interventions are revolving around spike protein. However, emphasizing on envelope protein's (1) conserved epitopes, (2) pathogenicity attenuating mutations, and (3) mutations present in the deceased patients, as reported in our present study, new directions to the ongoing efforts of therapeutic developments against COVID-19 can be achieved by targeting envelope viroporin.

A systematic review on the efficacies and therapeutic interventions of homoeopathic medicines in combating viral disorders with implications in the currently undergoinghomoeopathic treatment efforts for SARS-CoV-2 infection (COVID-19)

The prevalence of Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) has undergone a historic transition from December 2019 to June 2020. Under the current circumstances, SARS-CoV-2 has become a key problem for the public health and economic steadiness of the global fraternity. Based on ample evidences from the global epidemiology of SARS-CoV-2 and MERS-CoV (Middle EastRespiratory Syndrome-Corona virus) scientists and physicians strappingly consider these viruses share structural and functional similarities of selected biologically active enzymes namely, 3CLpro, PLproand RdRp. Ultra-diluted homoeopathic medicine has the legacy to combat infectious as well as viral diseases since last two centuries. Thus, a systematic review on existing antiviral homoeopathic therapies was done in the current study and the need of appropriate clinical validation with proper in vitroas well as in vivostudies prior to make clinical endorsements in treating COVID-19 patients with homoeopathic medicines has been explained. A brief summary of the currently undergoing or recently completed homoeopathic treatments of COVID-19 has also been provided to attract many more similar homoeopathic treatment attempts to combat COVID-19.(AU)