Drugs in use can fight resistant smallpox viruses

Poxviruses, among which is the smallpox virus, are the largest viruses (230-300 nm) that have a very complex structure, which does not show the typical helical or icosahedral symmetry of most viral particles. habitual and that are transmitted with greater assiduity.

A new scientific advance has made it possible to study drugs that are currently in use to combat resistant viruses of these diseases. Thus, it has been discovered how poxviruses evade the natural defenses of human cells, identifying a new therapeutic approach that could be more durable than current treatments.

As published in the journal Nature, this is due to the discovery of how poxviruses take advantage of a cellular protein to evade the host cell’s defenses and thus replicate and spread efficiently.

Immunosuppressive drugs or drugs against other viral infections are directed against this cellular protein. The team discovered that these drugs can also restrict the replication and spread of poxviruses.

This treatment approach, in which the drug does not directly target the virus, means that it will be much more difficult for the virus to develop resistance to the drug. And since this mechanism of sequestration is the same in many poxviruses, the drugs will be effective in treating a number of diseases such as smallpox and monkeypox or monkepox (mpox).

Despite the fact that smallpox has been eradicated as a disease since 1979, the virus that causes it, variola, continues to be kept in two high-security laboratories: one in the United States and the other in Russia. The threat of the smallpox virus being used in bioterrorism has led to the approval of a drug, tecovirimat, to treat the infection.

Tecovirimat for severe cases

There is an epidemic of monkeypox (caused by the monkeypox virus): although the number of infections has decreased in the UK, it is still present, especially in London, and in many other countries.

In the past year, tecovirimat has been used to treat severe cases of monkeypox, but this has led to the emergence of multiple drug-resistant strains of monkeypox virus.

“The drugs we have identified may be more durable than current monkeypox treatment, and we hope they will also be effective against other poxviruses, including the one that causes smallpox,” says Professor Geoffrey L. Smith, who led the work. at the Department of Pathology at the University of Cambridge, the Dunn School of Pathology at the University of Oxford and the Pirbright Institute, in the United Kingdom.

host cell

Once a poxvirus infects a host cell, it has to defend itself against attack by cellular proteins that would restrict the replication and spread of the virus. The researchers identified a specific cell protein, called TRIM5alpha, that restricts the growth of the virus, and another cell protein called cyclophilin A that prevents TRIM5alpha from doing so. Existing drugs target cyclophilin A, making the virus more sensitive to TRIM5alpha.

“There are several drugs that target cyclophilin A, and since many of them have already gone through clinical trials, we would not start from scratch, but rather reuse existing drugs, which is much faster,” explains Smith.

“Our results were totally unexpected,” Smith acknowledges. We started research because we were interested in understanding the basic science of how poxviruses evade host defenses, and we had no idea that this could lead to drugs to treat monkeypox virus and other poxviruses.”

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