withaferin-a and Coronavirus-Infections

We are living through an unprecedented crisis with the rapid spread of the new coronavirus disease (COVID-19) worldwide within a short time. The timely availability of thousands of SARS-CoV-2 genomes has enabled the scientific community to study the origin, structures, and pathogenesis of the virus. The pandemic has spurred research publication and resulted in an unprecedented number of therapeutic proposals. Because the development of new drugs is time consuming, several strategies, including drug repurposing and repositioning, are being tested to treat patients with COVID-19. Researchers have developed several potential vaccine candidates that have shown promise in phase II and III trials. As of 12 November 2020, 164 candidate vaccines are in preclinical evaluation, and 48 vaccines are in clinical evaluation, of which four have cleared phase III trials (Pfizer/BioNTech's BNT162b2, Moderna's mRNA-1273, University of Oxford & AstraZeneca's AZD1222, and Gamaleya's Sputnik V vaccine). Despite the acquisition of a vast body of scientific information, treatment depends only on the clinical management of the disease through supportive care. At the pandemic's 1-year mark, we summarize current information on SARS-CoV-2 origin and biology, and advances in the development of therapeutics. The updated information presented here provides a comprehensive report on the scientific progress made in the past year in understanding of SARS-CoV-2 biology and therapeutics.

Topics: Adenosine Monophosphate; Alanine; Amides; Animals; Antiviral Agents; Chloroquine; Clinical Trials as Topic; Coronavirus; Coronavirus Infections; COVID-19; COVID-19 Vaccines; Drug Combinations; Drug Repositioning; Glucocorticoids; Humans; Hydroxychloroquine; Indoles; Ivermectin; Lopinavir; Mutation; Pandemics; Phytotherapy; Plant Extracts; Pyrazines; Ritonavir; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Tinospora; Viral Zoonoses

The outbreak and continued spread of the novel coronavirus disease 2019 (COVID-19) is a preeminent global health threat that has resulted in the infection of over 11.5 million people worldwide. In addition, the pandemic has claimed the lives of over 530,000 people worldwide. Age and the presence of underlying comorbid conditions have been found to be key determinants of patient mortality. One such comorbidity is the presence of an oncological malignancy, with cancer patients exhibiting an approximate two-fold increase in mortality rate. Due to a lack of data, no consensus has been reached about the best practices for the diagnosis and treatment of cancer patients. Interestingly, two independent research groups have discovered that Withaferin A (WFA), a steroidal lactone with anti-inflammatory and anti-tumorigenic properties, may bind to the viral spike (S-) protein of SARS-CoV-2. Further, preliminary data from our research group has demonstrated that WFA does not alter expression of ACE2 in the lungs of tumor-bearing female mice. Downregulation of ACE2 has recently been demonstrated to increase the severity of COVID-19. Therefore, WFA demonstrates real potential as a therapeutic agent to treat or prevent the spread of COVID-19 due to the reported interference in viral S-protein to host receptor binding and its lack of effect on ACE2 expression in the lungs.

Topics: Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Betacoronavirus; Cachexia; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Female; Humans; Mice; Ovarian Neoplasms; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Receptor, Angiotensin, Type 1; RNA, Messenger; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Withanolides; Xenograft Model Antitumor Assays