5 Spike Protein Blocking Drugs Under Research for COVID-19

The article, How the Covid-19 Virus Tricks the Human Cell, talks about how the SARS-CoV-2 virus can attach to human cells using the receptors on the cellular surface. Once connected, the virus can enter the cells, multiply and cause cell and organ damage.

Using that knowledge, a drug that can block the S protein from attaching to a receptor can prevent infection of all the organs with that receptor.

Covid-19 has infected 2.79 million and killed 191 thousand based on the Johns Hopkins Dashboard. No definitive medicines for Covid-19 exist.

If drug companies start from scratch in developing new drugs, it may take years, and that is not acceptable. Using an existing and approved drug that is used for other clinical conditions may be a faster source of drugs.

To look for these potential drugs, scientists from different fields are using known information about the molecular structure of present medications to know the drug candidates. Using computer software and algorithms, they match the molecular structure of the drug against the S protein or the receptor. To make it work, they should have a perfect fit.

Below is a simplified view.

Docking_representation_2 — How a Drug (ligand) might block a protein (receptor) or enzyme

The cell receptors mentioned in this article are the ACE2, TMPRSS2, GRP78, and CD-147. Furin is not a receptor but is included here because it is needed for the S protein to attach to the ACE2 receptor.

Camostat

Camostat is a drug made by Ono Pharmaceutical. It has been approved by the Japanese FDA to use in chronic pancreatitis and post-operative reflux. A German study published recently in Cell showed that Camostat can block both the ACE2 and TMPRRS2 receptors.

ACE2 receptors are found on the lungs, heart, arteries, intestines, and kidneys.

TMPRSS2 are found in healthy and diseased tissue. The organs with TMPRSS2 are the small intestines, prostate, colon, stomach, and salivary gland.

Nafamostat

Nafamostat is a blood thinner used in critically ill patients with life-threatening clotting disorders (disseminated intravascular coagulation) and acute pancreatitis. In the laboratory, it can block the S protein from binding to the TMPRSS2 and ACE2. In a comparison between nafamostat and camostat, the camostat is ten-fold less active.

Meplazumab

Meplazumab is a humanized antibody that blocks the attachment of the spike protein of the SARS-CoV-2 to the CD-147 receptor. The CD-147 can be found in the inner lining of the blood vessels and intestines and white blood cells. In a clinical trial from China that was in medRxiv, the authors said,

Adding meplazumab 20–30 mg in patients with COVID-19 who have received recommended treatment, increased the virological clearance rate, promoted the recovery of chest radiographic and lymphocytopenia, decreased the inflammation index (CRP), accelerating the improvement of disease without serious adverse event.

Meplazumab is relatively new and is undergoing clinical trials as Covid-19 treatment.

BOLD-100

GRP78 (Glucose Regulatory Protein 78) is an essential protein found inside the cells of the body. Under certain conditions, GRP78 comes out and becomes a binding site for viruses like the SARS-CoV-2, as shown in this study.

BOLD-100 is a compound made by BOLD Therapeutics that decreases the amount of GRP78. According to drugtargetreview,

Bold Therapeutics is focused on the development of BOLD-100 in combination with FOLFOX and other anti-cancer agents for the treatment of various gastrointestinal cancers, including gastric, pancreatic, colorectal and bile duct (cholangiocarcinoma) cancers.

BOLD Therapeutics initiated a partnership with the University of Ottawa to investigate BOLD-100 for Covid-19.

Folic Acid

Furin is an enzyme that turns an inactive protein into its active form. For Covid-19, Furin allows the attachment of the S protein of the SARS-CoV-2 to the ACE2 receptor.

Based on a study from Iran in ChemRxiv, Folic acid can bind Furin. Once Furin is restricted, the SARS-CoV-2 will not be able to attach to the target cells. Folic acid is a vitamin B. It is safe and present in spinach, broccoli, asparagus, dried beans, lentils, peas, and oranges. Folinic acid is an active metabolite of folic acid. The authors concluded,

Thus, folic acid, as a safe drug, could be useful in the prevention or management of COVID-19-associated respiratory disease in the early stages of the (Covid-19) disease.

ice_screenshot_20200424-145722 — The folic and folinic acid shown on top is inserted and shown as purple sticks in between the Furin and ACE2 ribbon models.

MedRxiv, BioRxiv, and ChemRxiv is an internet repository of articles that are not yet peer-reviewed. Peer-review is a layer of scrutiny in the process of scientific journal publications to assure the quality of studies. That may take months sometimes.

There is an urgency about Covid-19 since there is no validated treatment, and information is needed. In that regard, non-peer-reviewed studies are being used by many other science websites.

This article may not include all the receptors and potential drugs for Covid-19. The purpose of this article is to provide hope that there are ongoing researches for treatment options for Covid-19.

The knowledge about Covid-19 is rapidly evolving. Information may update as new researches are done. Stay current by subscribing.

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