An ACE2, SARS-CoV-2 spike protein binding protein, -like enzyme isolated from food-related microorganisms.

Angiotensin-converting enzyme 2 (ACE2) is a binding target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. An ACE2-like enzyme, such as bacterial M32-carboxypeptidase (M32-CAP), is assumed to be a potential therapeutic candidate for coronavirus disease 2019 (COVID-19). Here, we screened bacteria with an ACE2-like enzyme activity from Japanese fermented food and dietary products using the fluorogenic substrate for rapid screening. The strain showing the highest activity, Enterobacter sp. 200527-13, produced an enzyme with the same hydrolytic activity as ACE2 on Angiotensin II (Ang II). The enzymatic analysis using the heterologously-expressed enzyme in Escherichia coli revealed that the enzyme catalyzes the same reaction with that of ACE2, Ang II hydrolysis to Ang 1-7, and phenylalanine. The gene sequence information showed that the enzyme belongs to the M32-CAP family. These results suggested that the selected enzyme, M32-CAP (EntCP), from Enterobacter sp. 200527-13 was identified as an ACE2-like enzyme.

COVID-19 After Treatment With Direct-acting Antivirals for HCV Infection and Decompensated Cirrhosis: A Case Report.

BACKGROUND: Eradication of hepatitis C virus (HCV) from chronic HCV-infected patients could improve liver function and prevent hepatocarcinogenesis in the long term. Eradication of HCV by direct-acting antivirals (DAAs) also leads to dynamic immunological changes. We report a case of recurrent coronavirus disease 2019 (COVID-19) that developed immediately after combination treatment with DAAs for HCV infection and decompensated cirrhosis. CASE REPORT: A 55-year-old male was started on a 12-week treatment with combination of HCV NS5A inhibitor velpatasvir and HCV NS5B polymerase inhibitor sofosbuvir. HCV RNA became undetectable after six weeks of treatment and was undetectable at the end of the treatment (EOT). Twelve days after the EOT, we diagnosed the patient with COVID-19 pneumonia, admitted him to our hospital and he was discharged two weeks later. One week after his discharge, he visited our hospital again, was diagnosed with recurrent COVID-19 pneumonia readmitted for a second time. Four days after second admission, cardiac arrest occurred, however, he recovered from severe COVID-19 and achieved sustained virological response and his liver function improved. CONCLUSION: In the COVID-19 era, while attention should be paid to the occurrence or exacerbation of infection, including COVID-19, interferon-free DAA combination therapy should be performed for HCV-infected individuals.