Reply To Ma And Wang: Reliability Of Various In Vitro Activity Assays On Sars-Cov-2 Main Protease Inhibitors

Ma and Wang (1) tested our recently reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) noncovalent inhibitors (2) using their in vitro assays, and they obtained negligible or much lower inhibitory activities compared to ours. Knowing the discrepancy, we first carefully rechecked our original experimental records, and we did not find any potential concern with our data that had been repeated by multiple coauthors. Notably, the fluorescence resonance energy transfer (FRET)-based enzymatic assay used by Ma and Wang (1) is different from our FRET-based enzymatic assay in the Mpro protein (discussed below) and the FRET substrate [longer than the more popularly used substrate (3, 4) utilized in our assay].\n\nParticularly for Mpro, Ma and Wang (1) incorrectly state that a GST-tagged Mpro was used in our assay. Actually, as … \n\n[↵][1]2To whom correspondence may be addressed. Email: zhan{at}uky.edu, wx8399{at}ouc.edu.cn, or luohb77{at}mail.sysu.edu.cn.\n\n [1]: #xref-corresp-1-1