Strong Inhibitory Activity and Action Modes of Synthetic Maslinic Acid Derivative on Highly Pathogenic Coronaviruses: COVID-19 Drug Candidate.

Raya Soltane,Mohamed A Ali,Ahmed A Al-Karmalawy,Ahmed Mostafa,Karim Chouaïb,Mahmoud Shehata,Ahlam Alasiri,Abdelwaheb Dhahri,Jawhar Gharbi,Rami Adel Pashameah,Amani Chrouda,Omnia Kutkat,Hichem Ben Jannet

doi:10.3390/pathogens10050623

Abstract

In late December 2019, a novel coronavirus, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), escaped the animal–human interface and emerged as an ongoing global pandemic with severe flu-like illness, commonly known as coronavirus disease 2019 (COVID-19). In this study, a molecular docking study was carried out for seventeen (17) structural analogues prepared from natural maslinic and oleanolic acids, screened against SARS-CoV-2 main protease. Furthermore, we experimentally validated the virtual data by measuring the half-maximal cytotoxic and inhibitory concentrations of each compound. Interestingly, the chlorinated isoxazole linked maslinic acid (compound 17) showed promising antiviral activity at micromolar non-toxic concentrations. Thoughtfully, we showed that compound 17 mainly impairs the viral replication of SARS-CoV-2. Furthermore, a very promising SAR study for the examined compounds was concluded, which could be used by medicinal chemists in the near future for the design and synthesis of potential anti-SARS-CoV-2 candidates. Our results could be very promising for performing further additional in vitro and in vivo studies on the tested compound (17) before further licensing for COVID-19 treatment.

Highlights

The whole world is suffering from a new evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originally spread from the Hubei region, concisely in Wuhan
By the end of January, and due to the increasing rate of SARS-CoV-2-infected confirmed cases associated with relatively high mortality rate, the WHO raised awareness and declared an emergency, claiming a potentially pandemic lethal infectious disease named COVID-19
SARS-CoV-2 was considered as a zoonotic disease, based on a high number of infected people exposed to a wet animal market in the Wuhan Chinese city; transmission from person to person was confirmed, making the situation even more harsh

Summary

Introduction

Coronavirus disease 2019 (COVID-19) has triggered a scary and contagious global pandemic of severe pneumonia-like disease, which causes respiratory illness and acute respiratory distress syndrome in human. 19 to minimize its awful spread and transmission [1] To this point, researchers have tried to make use of the existing anti-viral drugs that might combat the infection based on in and acuteor respiratory syndrome in human. The race is still on to silicoillness predictions, based ondistress previous knowledge of other coronaviruses such as SARSdiscover specific and efficient anti-viral drugs against SARS-CoV-2 to control COVID-19. A lot of FDA approved drugs have been tested or reposito minimize its awful spread and transmission [1] To this point, researchers have tried to tioned to act as anti-SARS-CoV-2 [2,3]. Several trials to virtually recommend make use of the existing anti-viral drugs that might combat the infection based on in silico or practically the anti-SARS-CoV-2 activity of synthetic compounds, natural extracts predictions,test or based on previous knowledge of other coronaviruses such as SARS-CoV and and immunomodulatory agents have attempted [4,5,6,7]

Methods

Results

Conclusion