Therapeutic Strategies to Kill COVID-19

Wired May 2020 pp20-21 “How To Kill A Coronavirus”. “Even a bug this ruthless has a few fatal weaknesses of its own” by Sara Harrison

Much attention has been focused on the ability to breakdown COVID-19’s fatty layer on surfaces like countertops, carboard, metal etc. with detergents and alcohol-based disinfectants. UV light is also know to destroy RNA and DNA. All of these solutions are for surfaces only.

What are the treatment strategies that are being considered for rendering the virus inactive within the body?

The in body or in vivo treatments must stop one or more steps in viral “life” cycle.

Like all viruses COVID-19 can’t “live” and reproduce without invading and taking-over the host cell machinery. Some key steps in this process are; 1) attaching to a human cell be it in the lung, small intestine or brain etc. 2) after attachment it must traverse the cell membrane 3) once inside the cell it usurps normal cell function to create additional viral particles that are then 4) pushed out the way they came.

Block step 1) Antibodies, proteins made by our immune system, can couple and effectively neutralize or block COVID-19’s attachment. These antibodies can be infused from recovered COVID-19 patients to patients with active disease or we can entice our own body to make these blocking antibodies by immunizing or vaccinating. Infusing plasma from recovered patients is cumbersome and impossible to scale but even in the absence of randomized clinical trials there is strong case-by-case data demonstrating dramatic life-saving benefit. To scale, researchers are working to isolate the B Cells, cells that make antibodies, from recovered patients, identify those B Cells making the most neutralizing antibodies, replicating those cells in culture and producing immortal humanized B Cell clones that can make antibody in unlimited quantities. It's not surprising that infusion of antibodies, called passive immunity, is effective as this has been borne out repeatedly throughout medical history. Vaccines have been successfully made for many viruses, like Hepatitis B but not for all viruses with Hepatitis C and HIV as recent examples. Producing safe and effective vaccines usually takes five to ten years but there’s hope that a global focus using old and new technologies will succeed in reducing this lead time. Another way to block COVID-19 entry is to saturate our bodies with proteins that bind the virus, just like the true viral target protein, but of course these proteins aren’t on a cell surface and don’t induce cellular uptake.

Block step 2) find agents that stops bound virus from entering the target cell. Attractive idea but these general or non-specific agents would also disrupt vital cell functions.

Block step 3) by keeping the viral genome from being replicated and or inhibit the production of key viral proteins. RNA therapeutics could act by mimicking RNA building blocks. Look-alike precursors that don’t build upon each other to form functional strands of RNA or by inhibiting enzymes that are required for making functional strands of RNA. Other drugs look to selectively inhibit the production of mature or functional viral proteins.

Block step 4) like 2) and as with all therapeutics, the dose required to inhibit the virus must not appreciably poison normal cell function.

Although, not directed at the virus, other therapies for COVID-19 are focused on reducing what may be an overstepping of the patient's immune response (cytokine storm). Tried on a case-by-case basis and awaiting more formal clinical trials are therapies that block the pro-inflammatory cytokine know as Interleukin-6. Anti-IL-6 and Anti-IL-6 receptor monoclonal antibodies are being investigated. "...patients with SARS-CoV-2 pneumonia" had remarkable benefit from anti-IL-6 receptor blockade. There are two such drugs already approved for other indications in America known as Tocilizumab and Sarilumab. (Source NCT04322773)

While all are hopeful for a vaccine and anti-viral therapies, the focus is also on immediate safeguards and treatment protocols.

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