Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives
Journal
Frontiers in pharmacology
Journal Volume
11
Date Issued
2020
Author(s)
Yang, Cheng-Wei
Lee, Yue-Zhi
Hsu, Hsing-Yu
Jan, Jia-Tsrong
Lin, Yi-Ling
Peng, Tzu-Ting
Yang, Ruey-Bing
Liang, Jian-Jong
Liao, Chun-Che
Pang, Yu-Hau
Kao, Han-Chieh
Huang, Wen-Zheng
Lin, Jiunn-Horng
Chang, Chun-Ping
Niu, Guang-Hao
Wu, Szu-Huei
Sytwu, Huey-Kang
Chen, Chiung-Tong
Lee, Shiow-Ju
Abstract
Tylophorine-based compounds and natural cardiotonic steroids (cardenolides and bufadienolides) are two classes of transmissible gastroenteritis coronavirus inhibitors, targeting viral RNA and host cell factors, respectively. We tested both types of compounds against two types of coronaviruses, to compare and contrast their antiviral properties, and with view to their further therapeutic development. Examples of both types of compounds potently inhibited the replication of both feline infectious peritonitis virus and human coronavirus OC43 with EC50 values of up to 8 and 16 nM, respectively. Strikingly, the tylophorine-based compounds tested inhibited viral yields of HCoV-OC43 to a much greater extent (7-8 log magnitudes of p.f.u./ml) than the cardiotonic steroids (about 2-3 log magnitudes of p.f.u./ml), as determined by end point assays. Based on these results, three tylophorine-based compounds were further examined for their anti-viral activities on two other human coronaviruses, HCoV-229E and SARS-CoV-2. These three tylophorine-based compounds inhibited HCoV-229E with EC50 values of up to 6.5 nM, inhibited viral yields of HCoV-229E by 6-7 log magnitudes of p.f.u./ml, and were also found to inhibit SARS-CoV-2 with EC50 values of up to 2.5-14 nM. In conclusion, tylophorine-based compounds are potent, broad-spectrum inhibitors of coronaviruses including SARS-CoV-2, and could be used for the treatment of COVID-19.
Subjects
COVID-19; FIPV; HCoV-229E; HCoV-OC43; SARS-CoV-2; coronavirus; ouabain; tylophorine
SDGs
Type
journal article