On the 23rd of July, 2022, the World Health Organization (WHO) announced that the Monkeypox outbreak is a Public Health Emergency of International Concern (PHIEC) with more than 16,000 reported cases in 75 countries and territories. Although they haven’t designated it as a pandemic, it is already high-alert for the world-wide public health system. American Actor Matt Ford, became one of the first public figures who confessed in social media that he got contracted with monkeypox. As a follow up for the ongoing stigma on this disease, WHO has established an open forum to rename the virus, and is already renaming the existing clades. Unlike the early phase of COVID-19 pandemic, the vaccine and drugs for monkeypox are available in limited supply. Herewith, we are going to examine the role of bioinformatics, as a relatively new field of study, on developing surveillance technology toward this emerging disease.
Bioinformatics is the application of computer science in life sciences. One of the unique applications of this new field is in molecular medicine and medical biotechnology research. Molecular phylogenetics is a bioinformatics method that is often deployed to determine the origin of virus, clusterization, and most importantly, detecting new viral variants and strains. Hence, the first human infection was known during an outbreak in Congo during the 70s. Based on molecular phylogeny studies, scientists found two clades with distinct mutation patterns, from Western and Central Africa. Hence, as for now, WHO is currently reconsidering to rename the clades to avoid stigma. While they are yet to determine the new name of the virus, the clades are renamed to ‘Clade I’ and ‘Clade II’ based on convention from that international body. The current outbreak in 2022 occurred due to the Clade II infection, with significant phylogenetic similarity with the previous outbreak in Africa during 2018-19. Based on in vivo (animal) studies and clinical observation, clade II is more virulent than the other. It is within the same genus with smallpox virus, the Orthopoxvirus.
How could bioinformaticians determine the current outbreak link with the previous one? How can they determine the clusterization of monkeypox virus into distinct clades? As aforementioned, the molecular phylogenetics method determined the clusterization of the virus sample using a bioinformatics algorithm such as neighbor-joining. In respect of the human sampling, after securing ethical clearance from the medical ethics committee, the healthcare professional isolates the sample from the patient, and prepares it for further processing. The essential information to determine the clade is the DNA sequences of the virus. Herewith, with the Next-Generation Sequencing (NGS) machine, the sequences could be obtained from the sample. Then, the bioinformatics method was deployed to determine the clades with molecular phylogenetics software. There, the clades information could be retrieved, and the nonsynonymous mutations that could elicit possible enhanced virus virulency could be identified.
What is another contribution of bioinformatics in dealing with monkeypox outbreak? Besides the advanced surveillance method, do they contribute in other areas such as drug development? Structural biology is the branch of biology that studies the dynamics and structure of biological macromolecules such as DNAs and proteins. Structural biologists have crystallized a certain protein structure of monkeypox, namely the A42R protein. It is an important protein that is related to phosphoinositide metabolism. It was crystallized by the Center for Structural Genomics of Infectious Diseases (CSGID), a consortium of American universities working in structural biology, in 2014. As for now (18th of August, 2022). It is the only monkeypox virus protein structure in the RCSB database, a central world-wide database that gathers structural biology experimental results. As the structural biology experimentation is still in progress to gather more information on monkeypox virus protein structures, bioinformaticians are looking for alternative methods to propose drug candidates. Structural bioinformatics, another branch of this emerging field, is the application of structural biology in bioinformatics. Structural bioinformaticians are strategizing with modeling the in-silico drug repurposing efforts with vaccinia virus proteins, which are closely related with monkeypox virus. Drug development efforts for monkeypox are ongoing as the existing drug such as tecovirimat (TPOXX), could only be deployed for distinct clinical conditions such as people that are severely ill. TPOXX is a repurposed drug from already-eradicated smallpox disease. They repurposed it as smallpox and monkeypox are closely related. In this regard, scientists are still looking for better alternatives.
Two bioinformatics branches, namely molecular phylogenetics and structural bioinformatics, have elicited significant contributions in dealing with the current monkeypox outbreak. The scientists in these fields could give sufficient information about the outbreak to the WHO, along with the solid support from medical biotechnologists, so they can declare the PHIEC. In the end, it is necessary for us to adhere to the WHO’s guidelines in this matter, that is adapted by their respective members as well.
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