The main protease, M^pro(or 3CL^pro) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide. Feline infectious peritonitis, a fatal coronavirus infection in cats, was successfully treated previously with a prodrug GC376, a dipeptide-based protease inhibitor. Here, we show the prodrug and its parent GC373, are effective inhibitors of the M^profrom both SARS-CoV and SARS-CoV-2 with IC₅₀values in the nanomolar range. Crystal structures of SARS-CoV-2 M^prowith these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 replication in cell culture. They are strong drug candidates for the treatment of human coronavirus infections because they have already been successful in animals. The work here lays the framework for their use in human trials for the treatment of COVID-19.

Helicobacter pylori (H. pylori) (formerly known as Campylobacter pyloridis) has been studied for over a century due to its association with peptic ulcer disease and gastric cancer. Its prevalence has been declining due to improvements in hygienic conditions and effective curative and preventive approaches. However, it is still present in different communities and continues to spread, increasing its global presence in both developing as well as developed countries. Extensive research has been ongoing to eradicate this pathogen, and at present, scientists have discovered different management options. This article highlights the global prevalence of H. pylori infection and the factors responsible for its transmission, treatment regimens, and prevention.

The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin–binding proteins, is fundamentally important in eukaryotes. α-Actinins are major F-actin bundlers that are inhibited by Ca²⁺ in nonmuscle cells. Here we report the mechanism of Ca²⁺-mediated regulation of Entamoeba histolytica α-actinin-2 (EhActn2) with features expected for the common ancestor of Entamoeba and higher eukaryotic α-actinins. Crystal structures of Ca²⁺-free and Ca²⁺-bound EhActn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of the EhActn2 CaMD for Ca²⁺, binding of which can only be regulated in the presence of physiological concentrations of Mg²⁺. Ca²⁺ binding triggers an increase in protein multidomain rigidity, reducing conformational flexibility of F-actin–binding domains via interdomain cross-talk and consequently inhibiting F-actin bundling. In vivo studies uncover that EhActn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery.

The highly conserved G-M-N motif of the CorA-Mrs2-Alr1 family of Mg2+ channels has been shown to be essential for Mg2+ transport. We performed random

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