Potential Treatment of Monkeypox

We are in the midst of a monkeypox pandemic, and as monkeypox continues to evolve, so must our methods of prevention, control, and treatment. Currently, there is no treatment specifically approved for monkeypox virus (MPXV) infection. However, due to the genetic similarity between MPXV and the smallpox virus, antiviral drugs and vaccines for smallpox may be beneficial for monkeypox treatment.

Creative Biolabs provides resources to help our clients gain insight into these potential therapies and offers drug discovery platforms and drug discovery solutions to help pharmaceutical companies that will utilize these therapies to address the monkeypox pandemic in the future.

Searching for Repurposed Antiviral Drugs

There are two main types of antiviral drugs used to treat smallpox that can be recommended for monkeypox treatment. One drug works by targeting the viral VP37 protein to stop the virus from spreading in the body. The second drug works by inhibiting the viral DNA polymerase enzyme.

Fig. 1 Chemical structures of two antiviral drugs. (Obeid M A, et al., 2022)3

• The first drug is a small molecule viral export inhibitor that was developed to target a protein used by other orthopoxviruses, including MPXV, so scientists believe it could also tame monkeypox. Its chemistry comprises of carbotricycle moiety as well as a hydrazine. It acts as an envelope protein inhibitor that prevents the virus from leaving the infected cell and the spread of the virus within the host. It is effective in preclinical studies in animal models of monkeypox infection. Clinical trials of the drug are currently underway.
• The second drug is an orally bioavailable lipid acyclic nucleoside phosphonate with anti-acne virus activity. It is approved for the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). It has been shown to be effective against orthopoxviruses in animal models. However, clinical data on its efficacy against human monkeypox are lacking.

In addition to repurposing smallpox antivirals, several researchers are racing to discover new antivirals for the treatment of monkeypox. They are screening candidate anti-monkeypox drugs from a library of clinically approved antiviral, antifungal, and antiparasitic drugs. Identified drug candidates include, but are not limited to:

• Atovaquone
• Mefloquine
• Molnupiravir
• C-CA3-ADO
• C3-NPC A
• Ribavirin
• Tiazofurin

Developing Monoclonal Antibodies

Currently, seriously ill or immunocompromised monkeypox patients can be treated with intravenous vaccinia immune globulin intravenous (VIGIV), an antibody to orthopoxviruses collected from an immune host. It is approved for the treatment of rare smallpox vaccine side effects. However, there is no evidence that it is effective against monkeypox.

Researchers now focus on developing monoclonal antibodies with higher specificity and activity. This is because monoclonal antibodies provide fast, long-lasting, and effective protection.

The high human-to-human transmission nature of the 2022 monkeypox outbreak suggests that this may not be a transient epidemic. This may require new treatments and drugs to prevent and treat monkeypox infections. Facing the increasing number of monkeypox infections, we should probably develop an effective vaccine to prevent it. Rapid and effective mRNA vaccine development would be a viable option.