The COVID-19 pandemic is now entering its third year, and in addition to vaccines that can effectively prevent viral infections, scientists have been working to find "special drugs" that can act as a cure.

Eleven COVID-19 therapeutic drug therapies are currently available globally, including eight injectable drug therapies and three oral drugs, with two drug submitted to NDA. The COVID-19 drugs available in the U.S. include four small molecule drugs and four neutralizing antibody therapies.

There are 2 main technical routes of global COVID-19 drug development.

The first is the antibody-based biomacromolecular drug. The structure of COVID-19 virus is simple, a protein shell wrapped around the genetic material RNA. The spike protein on the surface of the virus acts as a "claw" and allows entry into the human cell by grasping a receptor on the surface of the human cell called ACE2 and enabling viral replication. Neutralizing antibodies are able to recognize and bind to the specific "claws" on the surface of the virus, preventing the virus from binding to the human cell in advance.

The second is small-molecule oral drugs, including Merck's Molnupiravir and Pfizer's Paxlovid, as well as Shionogi's S-217622 (The U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for S-217622).

If neutralizing antibody drugs are used to stop viruses from entering cells, then small-molecule oral drugs are used to disrupt virus replication.

Once viruses successfully invade a cell, their protein shells dissolve and release the genetic material RNA. The RNA then finds ways to replicate the virus, and the viral army is replicated and goes on to infect other healthy cells. In order to inhibit viral replication, small molecule oral drugs are created.

Which is better, neutralizing antibody drugs or small molecule oral drugs?

Neutralizing antibody drugs: better safety, limited capacity

Neutralizing antibody drugs can reduce viral load, reduce symptoms and lower hospitalization rates, and have a good safety profile. On May 26, 2021, Sotrovimab is authorized for use under an Emergency Use Authorization (EUA) for the treatment of mild-to-moderate  COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death. Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression. No safety signals were identified. After the discovery of the Omicron variant, GSK announced that experiments on cells suggest that sotrovimab will remain effective against it.

However, the disadvantages of neutralizing antibody drugs are also obvious. Most of the drugs are administered by injection, which is not convenient for ambulatory patients with minor illnesses. Furthermore, neutralizing antibody drugs are costly, difficult to deal with virus mutations, and require cold-chain transportation, and may be ineffective against certain mutated strains, making them difficult to be widely used for early prevention and control.

Small molecule oral drugs: easy to administer, high R&D costs

New drug development is similar to a big gamble, facing many uncertainties such as long lead time, high cost and high risk.

Although the cost of research and development is high, small-molecule oral drugs are easy to achieve large-scale production. Compared to neutralizing antibodies, small molecule oral drugs are more convenient to use. For example, Paxlovid treatment requires three oral tablets, two nirmatrelvir and one ritonavir, to be taken orally twice daily for five days, and cannot be used continuously for more than five days. Further, small molecule oral drugs have diverse mechanisms of action and can inhibit and block viral replication and transmission at multiple points.

Of course, there are disadvantages to small molecule oral drugs. Many small-molecule drugs are effective at suppressing the virus in in vitro trials, but their efficacy in in vivo clinical trials has been less than satisfactory.

There are also safety issues. Unlike intravenous drugs, which are used in hospitals, oral drugs, such as Molnupiravir, are used in home isolation for mild to moderately ill patients who lack medical supervision and may not be able to be transported to a doctor in time if serious side effects occur.

There is another obvious difference between neutralizing antibody drugs and small molecule oral drugs - price. Because of the high protein demand for neutralizing antibody drugs, not only is production capacity limited, but prices have also risen. According to U.S. government procurement prices, Pfizer's small-molecule oral drug Paxlovid costs $530 per course of treatment, while Eli Lilly's neutralizing antibody combination therapy is priced at $2,100, a nearly fourfold difference.

In front of the common enemy of all mankind, pharmaceutical research and development institutions and companies all over the world are working around the clock to develop effective drugs. Huateng Pharma has also contributed its share of strength. We can  provide CDMO services for COVID-19 drugs with sufficient capacity.

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