SARS-CoV-2

The SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) that is known to transmit through aerosols and contact surfaces has spread across the globe. It is now a pandemic, adversely affecting all daily life. Non-essential personnel are advised to wear a mask and maintain social distancing, whereas more responsible governments have made mandatory lockdown protocols. A significant portion of the warriors fights the virus by staying at home. Others at the forefront of the battle such as healthcare workers and researchers are constantly at work to find a cure for the coronavirus.

 Related blog posts: (links)

Current strategies in the fight against the pandemic:

Targets: There are several structural components that make up the viral machinery of the nCoV-19 (novel coronavirus 2019; common name for the SARS-CoV-2). Some of these are studied as potential targets for treating COVID-19 (Coronavirus disease 2019):

1) The viral protease: The RNA within the virus is actively translated inside the host cells by ribosomes. The major products of this process are the viral replication machinery (including the protease) and envelope proteins. The viral protease that is generated, uses host cell resources and aids in the replication of the viral RNA. The end products are then packed in well-constructed vesicles holding viral envelope proteins and replicated viral RNA within it. Studying the structure of the protease is helpful since it can be targeted to stop the replication of the virus. Small-molecule inhibitors are computationally screened to dock the viral protein, thus working as a potential treatment for the viral pandemic.

nCoV19 trimeric spike glycoprotein;
prefusion-chains A, B, C from PDB 6VSB.
2) The spike protein: the lipid membrane of the virus has projecting receptors that look similar to the spikes on a crown and thus the name coronavirus (la corona is Spanish for 'the crown'). The spike protein binds to the human ACE2 receptor and activates a secondary signalling pathway that initiates membrane fusion. The cell engulfs the virus allowing the viral RNA to enter and carry out its replication. Designing inhibitors to the ACE2 receptor or the Spike protein would serve the purpose of curing the disease.
other non-exclusive targets include:
3) The ACE2 (angiotensin-converting enzyme 2) receptors: these human cell receptors are also potential targets since they are able to inhibit the activation of viral infusion into the cell. Inhibiting this receptor might cause unwanted side effects since the normal functioning of the body may get hampered. Yet non-competitive antagonists are a class of drugs that can be explored.

4) Other viral machinery: RNA polymerase, envelope proteins and a few others.

Drugs and Vaccines: Several FDA approved drugs have been clinically tested to inhibit the nCoV-19 protease, these are previously used drugs for examples,

1. Remdesivir (a nucleotide analogue used in treating Ebola),
2. Ribavirin (an essential antiviral drug most commonly used in treating HCV),
3. Hydroxychloroquine (HCQ, an anti-malarial drug used alongside azithromycin in treating malaria),
4. Avifavir (anti-viral Influenza drug),
5. Favipiravir (an anti-viral drug used to treat influenza)

Although these existing drugs aid the war against the virus, no groundbreaking solution has been devised to treat the disease completely. A few drugs have been computationally screened to inhibit the spike protein but are awaiting clinical approval.

[Update 1st May 2020] Remdesivir is now a potential drug for treating SARS-CoV-2 [1]

[Update 12th June 2020] Avifavir will now be used as an antiviral drug to treat COVID in Russia [1]

[Update 22nd June 2020] Favipiravir is now approved for distribution in India, will certainly help in fighting the infection. [1,2]
 
[Update 17th January 2021] Vaccines

Follow the blog for updates. 
 
Project: Network analysis of the SARS-CoV-2 machinery reveals...

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