Coronaviruses — drug discovery and therapeutic options

Abstract

In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections.

Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle

“…The virus‐specific nucleic acid sequences were detected in lung fluid, blood and throat swab samples in 15 patients and the virus that was isolated showed a typical coronavirus appearance under electron microscopy. Further research will be conducted to better understand the new coronavirus to develop antiviral agents and vaccines 4 …”

Quantitative structure‐activity relationship and molecular docking revealed a potency of anti‐hepatitis C virus drugs against human corona viruses

“…Middle East Respiratory Syndrome Coronavirus (MERS CoV) was first identified 4 years ago in the Kingdom of Saudi Arabia . This was the first emergence of a new epidemic outbreak since the Sever Acute Respiratory Syndrome Coronavirus (SARS CoV) that out broke in East Asia in late 2002 . While SARS fatality rate was 8%, MERS fatality rate was 36% (by 9th of November 2016, the number of laboratory confirmed infections was 1813 and the number of reported deaths was 645) .…”

Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus

“…Potential therapeutic drugs for MERS-CoV patients include available approved drugs with nonspecific properties, such as immunomodulators, small-molecule drugs with broad antiviral activity, repurposed FDA-approved small-molecule drugs that show activity against MERS-CoV in vitro (Table 3) ( 34 , 35 ), and newly developed monoclonal or polyclonal antibody therapies with specific activity against MERS-CoV (Table 4) ( 54 ). …”

“…Considering development times and manufacturing requirements for new products, repurposing of existing drugs might potentially facilitate a rapid response to outbreaks of emerging viruses (see Regulatory section for a discussion on repurposing). Other early-stage work on MERS-CoV therapeutics includes studies focusing on the essential viral replication steps of fusion, proteolysis, and RNA polymerization (Table 3) ( 54 ). …”