MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2

Abstract

Although the spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a worldwide pandemic, there are currently no virus-specific drugs that are fully effective against SARS-CoV-2. Only a limited number of human-derived cells are capable of supporting SARS-CoV-2 replication and the infectivity of SARS-CoV-2 in these cells remains poor. In contrast, monkey-derived Vero cells are highly susceptibility to infection with SARS-CoV-2, although they are not suitable for the study of antiviral effects by small molecules due to their limited capacity to metabolize drugs compared to human-derived cells. In this study, our goal was to generate a virus-susceptible human cell line that would be useful for the identification and testing of candidate drugs. Towards this end, we stably transfected human lung-derived MRC5 cells with a lentiviral vector encoding angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV-2. Our results revealed that SARS-CoV-2 replicates efficiently in MRC5/ACE2 cells. Furthermore, viral RNA replication and progeny virus production were significantly reduced in response to administration of the replication inhibitor, remdesivir, in MRC5/ACE2 cells compared with Vero cells. We conclude that the MRC5/ACE2 cells will be important in developing specific anti-viral therapeutics and will assist in vaccine development to combat SARS-CoV-2 infections.

Iota-Carrageenan Inhibits Replication of SARS-CoV-2 and the Respective Variants of Concern Alpha, Beta, Gamma and Delta

“…Carrageenans not only have antiviral properties but also exert antitumor, immunomodulatory and coagulative activities, respectively [58][59][60][61][62][63][64][65][66][67][68][69][70][71]. In this context, it was published that kappa-and lambda-carrageenans exhibit both anticancer and immunostimulatory effects [58][59][60][61][62][63][64][65][66][67][68][69][70].…”

“…Carrageenans not only have antiviral properties but also exert antitumor, immunomodulatory and coagulative activities, respectively [58][59][60][61][62][63][64][65][66][67][68][69][70][71]. In this context, it was published that kappa-and lambda-carrageenans exhibit both anticancer and immunostimulatory effects [58][59][60][61][62][63][64][65][66][67][68][69][70]. In contrast, such immunomodulating and antitumoral effects have not been described yet for iota-carrageenan, supporting a broad application as an otherwise biologically inert substance.…”

Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro

“…The angiotensin-converting enzyme (ACE2) is expressed in Caco-2, Calu-3, and Vero-6 cells on the apical membrane domains [109,110]. A study investigated a library of thousands of marketed drugs and prototypes to evaluate the inhibition of virus-induced cytotoxicity using Caco-2 cell lines from human epithelial colorectal adenocarcinoma and SARS-CoV-2 obtained from a patient originally infected with the virus in Wuhan, China.…”

SARS-CoV-2 Permissive glioblastoma cell line for high throughput antiviral screening

“…Major efforts are ongoing to develop novel therapeutics for COVID-19 treatment and/or effective prophylactic approaches to prevent viral spread ( Yadav et al, 2021 ). In the context of early preclinical studies for SARS-CoV-2 antiviral assessment, screening platforms for drug libraries rely on the use of robust cellular infection systems, mostly based on immortalized cell lines originating from respiratory, but most often non-respiratory, tissues ( Murgolo et al, 2021 ; Uemura et al, 2021 ; Chiu et al, 2022 ; Ramirez et al, 2021 ; Grau-Exposito et al, 2022 ; Ko et al, 2021 ; Chu et al, 2020 ). In fact, many initial screenings for SARS-CoV-2 antivirals have largely utilized the African green monkey kidney cell line Vero E6 as the host cell.…”