CNS damage and Drug therapeutics for Sars-Cov-2.

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

We utilized the knowledge of medicinal plants used by native tribes of India to examine phytochemicals for their potential to inhibit respiratory coronaviruses including Human Coronavirus OC43 (HCoV-OC43) and SARS-CoV-2. We found four phytochemicals that inhibited both viruses in vitro and further tested one compound, Rottlerin (RTL), in a mouse model of SARS-CoV-2 infection. RTL significantly reduced SARS-CoV-2-induced mortality by 40% in human angiotensin-converting enzyme 2 (ACE2)-expressing K18 mice, showing efficacy in vivo. These studies were published in the International Journal of Antimicrobial Agents (Ojha, D., Jessop, F., Bosio, C.M., Peterson K.E. 2023. Effective inhibition of HCoV-OC43 and SARS-CoV-2 by phytochemicals in vitro and in vivo. Int J Antimicrob Agents. 2023 Jun 18;62(3):106893. doi: 10.1016) Our second project involves a collaborative project with Dan Chertow's group at the Clinical center in analyzing localization of virus in different tissues from Covid-19 autopsy patients. We collaborated with efforts to examine virus infection within the central nervous system. We have stained brain tissues sections from these patients to examine if SARS-CoV-2 infects the CNS and what cells are infected. We found infection of neurons by immunohistochemistry in multiple regions of the brain in multiple patients. This study was published in Nature (Stein et al. 2022. SARS-CoV-2 infection and persistence throughout the human body and brain at autopsy. Nature. 612:758-763. doi: 10.1038/s41586-022-05542-y).