Cyclophilin A and CD147: novel therapeutic targets for the treatment of COVID-19

Abstract

The outbreak of pneumonia caused by a new coronavirus (SARS-CoV-2) occurred in December 2019, and spread rapidly throughout the world. There have been other severe coronavirus outbreaks worldwide, namely, severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV). Because the genetic diversity of coronaviruses renders the design of vaccines complicated, broad spectrum-anti-coronavirus drugs have become a critical approach to control the coronavirus epidemic. Cyclophilin A is an important protein needed for coronavirus replication, and its inhibitor cyclosporine A has the ability to suppress coronavirus on a broad spectrum. CD147-S protein was found to be one route by which SARS-CoV-2 invades host cells, while CD147 was found to play a functional role in facilitating the infection of host cells by SARS-CoV. The CyPA/CD147 interaction may play a critical role in the ability of the SARS-CoV-2 virus to enter the host cells. However, cyclosporine A has immunosuppressive effects, so the conditions for its use as an antiviral drug are limited. As a result, cyclosporine A analogues without immunosuppressive side effects have attracted lots of interest. This review primarily discusses the drug development prospects of cyclophilin A as a therapeutic target for the treatment of coronavirus infection, especially coronavirus disease 2019 (COVID-19), and non-immunosuppressive cyclosporine analogues.

A review on possible mechanistic insights of Nitazoxanide for repurposing in COVID-19

“…A newer entry pathway identified is the Cluster of differentiation 147 (CD147) receptor-mediated entry which proceeds through the activation of its catalytic domain by integrins and matrix metalloproteinases (MMPs), essential for S-protein binding ( Gabison et al, 2005 ; Han et al, 2008 ; Liu and Zhu, 2020 ; Ulrich and Pillat, 2020 ). Nitazoxanide through its effect on PDI could inhibit activation of MMPs by blocking the cysteine switch mechanism ( Bonacci et al, 2011 ; McCarthy et al, 2008 ; Van Wart and Birkedal-Hansen, 1990 ) to prevent such entry.…”

ACE2: from protection of liver disease to propagation of COVID-19

“…Further the recombinant full ectodomains and the S1 domain of the viral spike protein do not interact with the basigin expressed on HEK293 cell lines. Importantly, a basigin ligand CyPA is needed for SARS-CoV replication raising a functional interaction and suggests that CyPA may also participate in SARS-CoV-2 infection [163]. Can these apparent disparate results be explained?…”

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

“…Basigin represents an attractive medical target because therapeutic agents have already been developed that target basigin based on basigin's previously-established role as an essential host receptor for invasion of the malaria parasite Plasmodium falciparum 11,12 . The claim that basigin acts as a host receptor for SARS-CoV-2 has already featured in published articles discussing the prioritization of therapeutics 13 , and has been the subject of published analyses looking at basigin expression on the assumption that it serves as a viral entry factor [14][15][16] .…”