Barbara Gatto

Abstract Although the connection between COVID-19 and coagulopathy has been clear since the beginning of SARS-CoV-2 pandemic, the underlying molecular mechanisms remain elusive. Available data support that the hyper-coagulant state is sustained by systemic inflammation. Here we show that the SARS-CoV-2 main protease (Mpro) can play a direct role in the activation of coagulation. Adding Mpro to human plasma increased clotting probability by 3-fold.

Abstract Many enzymes work as homodimers with two distant catalytic sites, but the reason for this choice is often not clear. For the main protease Mpro of SARS-CoV-2, dimerization is essential for function and plays a regulatory role during the coronaviral replication process. Here, to analyze a possible allosteric mechanism, we use X-ray crystallography, native mass spectrometry, isothermal titration calorimetry, and activity assays to study the interaction of Mpro with three peptide substrates.

Introduction Being the first class of chemotherapeutics, alkylating agents have played a major role in the treatment of cancer.1 One of the simplest representatives is mechlorethamine, which has been developed in the mid-20th century and is still in use today.2, 3 Its mode of action involves the intramolecular formation of a highly reactive aziridinium ion, by substitution of the chloride.