In-depth Bioinformatic Analyses of Human SARS-CoV-2, SARS-CoV, MERS-CoV, and Other Nidovirales Suggest Important Roles of Noncanonical Nucleic Acid Structures in Their Lifecycles

Martin Bartas; Václav Brázda; Natália Bohálová; Alessio Cantara; Adriana Volná; Tereza Stachurová; Katerina Malachová; Eva B. Jagelská; Otília Porubiaková; Jirí Cerven; Petr Pecinka

Remdesivir is an adenosine analogue that incorporates into nascent viral RNA chains and results in premature termination. Preliminary data have shown that remdesivir effectively inhibited virus infection in a human liver cancer cell line . Chloroquine is a potential broadspectrum antiviral drug and it already has been widely used as a low-cost and safe anti-malarial and autoimmune disease drug for more than 70 years. Application of chloroquine causes elevation of endosomal pH and also interferes with terminal glycosylation of the cellular receptor ACE2. This probably has a negative influence on virus-receptor binding and abrogates the infection (Vincent et al., 2005) . Drug repurposing seems like a very good strategy for quickly and at low cost finding a new therapy for new human diseases (Oprea and Mestres, 2012) . To date, there are few substances with Gquadruplex stabilizing features. One example is topotecan (also known by its brand name Hycamtin ® ), which frequently is used for treating ovary cancer. If everything else fails, it seems to be an option. On the other hand, topotecan cause unpleasant side effects, such as nausea, vomiting, and diarrhea (Topotecan -Chemotherapy Drugs -Chemocare). Many studies have described strong G-quadruplex stabilization effects (Li et al., 2018; Satpathi et al., 2018) , which might be one possible mode of action.