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China coronavirus: mild but infectious cases may make it hard to control outbreak, report warns

BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m325 (Published 28 January 2020) Cite this as: BMJ 2020;368:m325

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Re: China coronavirus: mild but infectious cases may make it hard to control outbreak, report warns

Dear Editor,

Earlier we postulated that ACE inhibitors and/or ARBs (angiotensin II receptor blockers) might be general viral antidotes (PMID: 15379656). ACE (CD143) appears on the macrophage plasma membrane during activation, the macrophage initiates the innate immune response, and many cell types involved in the innate immune response (lymphocytes, neutrophils, etc.) contain angiotensin II type 1 and/or type 2 receptors on their plasma membrane. Inhibiting ACE could therefore attenuate the severity of the "cytokine storm" responsible for morbidity and mortality in viral diseases. This approach may not apply to the herpes viruses, which induce a state of immunosuppression. But losartan, an ARB, seemed to lessen symptoms in humans, horses, and raptors infected with West Nile virus (ref. above and unpublished data).

The SARS coronavirus may offer a 2nd reason for using an ACE inhibitor or ARB (PMC2042929), depending on the patient's blood pressure. The virus binds to host cells via its spike glycoprotein, also called the E2 glycoprotein precursor (Gene ID 1489668; NCBI Accession number NP_828851.1). A peptide sequence within the binding domain (pfam09408, ABE77216) consists of (545)FQPFQQF(551). FQP is an analog of quinapril, an ACE inhibitor.

The cellular receptor for the spike glycoprotein is ACE2 (Gene ID: 59272). Like ACE, ACE2 has the same ancient zinc-binding catalytic site: (374)HEMGH(378). A potential autoinhibitory peptide exists downstream: (523)FQFQ(528). This is similar to ACE, a duplicated enzyme (ACE2 is not duplicated), in which the N-terminal active site has a potential autoinhibitory tripeptide 213 aa's C-terminal to it (FQP), analogous to quinapril, whereas the C-terminal active site has FKP, lisinopril, 213 aa's downstream.

The active site of ACE2 appears to bind both angiotensin II and the SARS coronavirus spike glycoprotein through an FQ-containing motif shared by quinapril. The active site of ACE2 thus resembles the N terminal active site of ACE. In patients lacking the systemic blood pressure for an ACE inhibitor like quinapril, an ARB such as losartan could be substituted as a first approximation, since we found it useful for West Nile virus encephalitis.

Competing interests: No competing interests

28 January 2020
David W Moskowitz MD
Physician
GenoMed, Inc.
Hollywood, Florida 33021