The broad-spectrum antiviral recommendations for drug discovery against COVID-19

Abstract

Despite to outbreaks of highly pathogenic beta and alpha coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus, the newly emerged 2019 coronavirus (COVID-19) is considered as a lethal zoonotic virus due to its deadly respiratory syndrome and high mortality rate among the human. Globally, more than 3,517,345 cases have been confirmed with 243,401 deaths due to Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19. The antiviral drug discovery activity is required to control the persistence of COVID-19 circulation and the potential of the future emergence of coronavirus. However, the present review aims to highlight the important antiviral approaches, including interferons, ribavirin, mycophenolic acids, ritonavir, lopinavir, inhibitors, and monoclonal antibodies (mAbs) to provoke the nonstructural proteins and deactivate the structural and essential host elements of the virus to control and treat the infection of COVID-19 by inhibiting the viral entry, viral RNA replication and suppressing the viral protein expression. Moreover, the present review investigates the epidemiology, diagnosis, structure, and replication of COVID-19 for better understanding. It is recommended that these proteases, inhibitors, and antibodies could be a good therapeutic option in drug discovery to control the newly emerged coronavirus.

Highlights

• COVID-19 has more than 79.5% identical sequence to SARS-CoV and a 96% identical sequence of the whole genome of bat coronaviruses.

• Acute respiratory distress syndrome (ARDS), renal failure, and septic shock are the possible clinical symptoms associated with COVID-19.

• Different antivirals, including interferons, ribavirin, lopinavir, and monoclonal antibodies (mAbs) could be the potent therapeutic agents against COVID-19.

• The initial clinical trials on hydroquinone in combination with azithromycin showed an admirable result in the reduction of COVID-19.

• The overexpression of inflammation response, cytokine dysregulation, and induction of apoptosis could be an well-organized factors to reduce the pathogenicity of COVID-19.

Keywords:

• COVID-19
• acute respiratory distress syndrome
• spike protein
• interferons
• treatment
• chloroquine
• Favipiravir
• nucleocapsid protein

Acknowledgement

Hereby, we extend our gratitude to A.Q Research Group and Prof. Dr Khalil-ur-Rahman for reviewing the article and providing helpful comments.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Glossary

Achilles heel: A recently revealed scoop on the surface of viruses that cause several infections, including the common cold, and a conceivable target for operative drugs

ACE2: Angiotensin-converting enzyme 2 (ACE2) is an enzyme that is attached to the outer layer (cell membrane) of cells in the heart, lungs, kidney, and intestine, and also help in the binding of drugs to infected cells for treatment. ACE2 also serves as the entry point into cells for some coronaviruses.

Beta-coronaviruses: Beta-coronaviruses are one of four genera of coronaviruses of the subfamily Orthocoronavirinae. They are enclosed, positive-sense, single-stranded RNA viruses of zoonotic origin and 2019-nCoV is of the B lineage

Camostat: Camostat is known as a serine inhibitor. It approved for several chronic diseases like pancreatic and postoperative reflux, but recently it showed significant results against SARS-CoV.

DAAs (direct-acting antivirals): Direct-acting antivirals (DAAs) are a comparatively novel class of medication that acts to target specific steps in the viral life cycle. The goals of DAAs are to target the virus and improve sustained virologic response (SVR) rates.

Furin: Furin is a protein that in humans is encoded by the FURIN gene, it synthesizes as inactive protein and activated by an inhibitor for proper function

Monoclonal antibodies (mAbs): Monoclonal antibodies are assembled due to identical immune cells that are all clones of a unique parent cell.

Nonstructural proteins (nsps): In virology, nonstructural proteins are those proteins that are coded my virus genome and help in the expression of viral genes during the replication of viruses.

Protease: The protease belongs to the family of enzymes which catalyzed the proteolysis by breaking the peptide bonds between protein and release a molecule of water in return.

Reverse genetic system: The reverse genetic system is a system in molecular genetics, which facilitate in the function of any gene via identified its phenotypic effect on precise nucleic acid sequences

Author contribution statement

Abu Hazafa, and Khalil-ur-Rahman conceived the presented data. Nazish Jahan, Abu Hazafa, Ikram-ul-Haq, and Muhammed Mumtaz developed the theory and performed the computations. Huma Naeem, Muhammad Farman, and Faheem Abbas helped to draw the artwork. Abu Hazafa and Khalil-ur-Rahman investigate and supervised the review. Sania Sadiqa, Muhammed Naeem, and Saira bano helped in revision. All authors provided critical feedback and helped shape the analysis and manuscript.

Informed consent

For this type of study informed consent is not required.