One of the most horrible diseases in history, Smallpox is caused by the Variola from Poxvirus family, has caused great morbidity and mortality along the way since it was eradicated in the 20th century. During and after the eradication program for Variola, other Poxviruses such as the Monkeypox (Mpox) virus, which causes a smallpox-like disease, became flagrant. With its long range of enzymes and proteins, poxviruses are effectively resisting hostile immune system attacks and disrupting cell signaling pathways. After Smallpox vaccination, cross-reaction immunity develops between Orthopoxviruses. Mpox is indeed an African endemic virus; however, increasing and emerging cases have been reported globally in recent years. According to Smallpox eradication in the 1970s and vaccination ceasing, nowadays centerpieces of the world population are vulnerable to Mpox virus. Our knowledge of Mpox is severely limited due to the lack of regular surveillance methods. Increasing education, boosting surveillance, and developing diagnostic competence is the most significant policies for improving identification, treatment, and restricting further virus spread. So Mpox can play a double-edge blade role in which without monitoring and increasing awareness it could be horrific and with public awareness and boosting surveillance it could be a paper tiger. This article reviewed previous reports about the Mpox merge from PubMed and google scholar from 2018 to June 2022.
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