Reductionism Ad Absurdum: The Misadventures of Structural Biology in the Time of Coronavirus

Abstract

The tragic consequences of the COVID-19 pandemic have led to admirable responses by the global scientific community, including a profound acceleration in the pace of research and exchange of findings. However, this has had considerable costs of its own, as erroneous conclusions have propagated faster than researchers have been able to detect and correct them. We illustrate the specific misunderstandings that have resulted from reductionist approaches to the study of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which are but one instance of a regrettably growing trend in structural biology. Far from merely being cautionary tales about the conduct of scientific research, these errors have had significant practical impact, by hampering a correct understanding of RdRp structure and mechanism, its inhibition by nucleoside analogues such as remdesivir, and the discovery and characterization of such analogues. After correcting these misunderstandings, we close with several recommendations for a broader correction of the course of scientific research.