Abstract Background Over the past few months, we have witnessed a new outbreak of a MPXV that has been detected without a clear link to Africa and has quickly spread globally. Methods In this article we investigate the mutational pattern of the MPXV and provide evidence for the presence of 6 new mutations that appear to characterize the current MPX-2022 outbreak. With the use of a number of chemical and physical parameters, we predict the stability of the mutated proteins, and propose an interpretation of the impact of these mutations on viral fitness). Findings Most mutations, particularly the Immunomodulator A46, TNFr and Large transcript constituent, affect proteins playing an important role in host response to MPVX infection and could also be relevant to the clinical features of the 2022 MPXV outbreak. Interpretation Although further, experimental work is necessary for a full understanding of the impact of the mutations here reported on virus replication pathways and host immunomodulation, our in-silico data suggest the importance of monitoring the emergence of new MPXV mutations for the prevention of future outbreaks potentially dangerous for public health. Funding No funding to declare

The evolution of Monkeypox virus: a genetic and structural analysis reveals mutations in proteins involved in host-pathogen interaction