Abstract
A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China at the end of 2019 causing a large global outbreak. As treatments are of the utmost importance, drug repurposing embodies a rich and rapid drug discovery landscape, where candidate drug compounds could be identified and optimized. To this end, we tested seven compounds for their ability to reduce replication of human coronavirus (HCoV)-229E, another member of the coronavirus family. Among these seven drugs tested, four of them, namely rapamycin, disulfiram, loperamide and valproic acid, were highly cytotoxic and did not warrant further testing. In contrast, we observed a reduction of the viral titer by 80% with resveratrol (50% effective concentration (EC50) = 4.6 µM) and lopinavir/ritonavir (EC50 = 8.8 µM) and by 60% with chloroquine (EC50 = 5 µM) with very limited cytotoxicity. Among these three drugs, resveratrol was less cytotoxic (cytotoxic concentration 50 (CC50) = 210 µM) than lopinavir/ritonavir (CC50 = 102 µM) and chloroquine (CC50 = 67 µM). Thus, among the seven drugs tested against HCoV-229E, resveratrol demonstrated the optimal antiviral response with low cytotoxicity with a selectivity index (SI) of 45.65. Similarly, among the three drugs with an anti-HCoV-229E activity, namely lopinavir/ritonavir, chloroquine and resveratrol, only the latter showed a reduction of the viral titer on SARS-CoV-2 with reduced cytotoxicity. This opens the door to further evaluation to fight Covid-19.
Highlights
Introduction published maps and institutional affilRenowned as rapidly evolving viruses, human coronaviruses (HCoVs) are positivestranded RNA pathogens that encompass seven different strains divided into two genera: alphacoronavirus and betacoronavirus [1]
Compounds were sourced from Sigma-Aldrich (St-Louis, MO, USA, resveratrol, chloroquine diphosphate), Pfizer, (New York, NY, USA, rapamycine), Sanofi (Paris, France, valproic acid or VPA, disulfiram), Abbott (Chicago, IL, USA, lopinavir/ritonavir) and Sandoz (Holzkirchen, Germany, loperamide)
We observed an antiviral effect of 50 μM lopinavir/ritonavir against high titers of HCoV-229E (MOI = 1) with approximately 80% inhibition of viral replication in vitro (Figure 1 and Table 1)
Summary
Introduction published maps and institutional affilRenowned as rapidly evolving viruses, human coronaviruses (HCoVs) are positivestranded RNA pathogens that encompass seven different strains divided into two genera: alphacoronavirus (alphaCoV) and betacoronavirus (betaCoV) [1]. Whilst alphaCoV includes the lowly pathogenic HCoV-229E and HCoV-NL63, betaCoV ramifies into the more pathogenic HCoV-OC43 and HCoV-HKU1 of the A lineage and the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 and the Middle East respiratory syndrome coronavirus (MERS-CoV) of the B and C lineage, respectively [2,3]. HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1 are endemic in human populations, accounting for 15–30% of mild, self-limiting respiratory upper infections, with a greater incidence of lower respiratory tract infection in immunocompromised individuals [4]. Both SARS-CoV, emerging in 2002 with a mortality rate of 9.6%, and MERS-CoV, responsible for the 2012 outbreak with a death rate of 35.5%, are linked to acute iations.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
