of these occur in East Africa, one in East Asia and one in Europe and North America. This suggests that the virus may have originated in East Africa. The most recent common ancestor of the Eurasian strains appears to have evolved ~60,000 years ago. The East Asian HSV-1 isolates have an unusual pattern that is currently best explained by the two waves of migration responsible for the peopling of Japan. Herpes simplex 2 genomes can be divided into two groups: one is globally distributed and the other is mostly limited to sub Saharan Africa. The globally distributed genotype has undergone four ancient recombinations with herpes simplex 1. It has also been reported that HSV-1 and HSV-2 can have contemporary and stable recombination events in hosts simultaneously infected with both pathogens. All of the cases are HSV-2 acquiring parts of the HSV-1 genome, sometimes changing parts of its antigen epitope in the process. The mutation rate has been estimated to be ~1.38×10−7 substitutions/site/year. In clinical setting, the mutations in either the thymidine kinase gene or DNA polymerase gene has caused resistance to aciclovir. However, most of the mutations occur in the thymidine kinase gene rather than the DNA polymerase gene. Another analysis has estimated the mutation rate in the herpes simplex 1 genome to be 1.82×10−8 nucleotide substitution per site per year. This analysis placed the most recent common ancestor of this virus ~710,000 years ago. Herpes simplex 1 and 2 diverged about . Treatment Similar to other herpesviridae, the herpes simplex viruses establish latent lifelong infection, and thus cannot be eradicated from the body with current treatments. Treatment usually involves general-purpose antiviral drugs that interfere with viral replication, reduce the physical severity of outbreak-associated lesions, and lower the chance of transmission to others. Studies of vulnerable patient populations have indicated that daily use of antivirals such as aciclovir and valaciclovir can reduce reactivation rates. The extensive use of antiherpetic drugs has led to the development of some drug resistance, which in turn may lead to treatment failure. Therefore, new sources of drugs are broadly investigated to address the problem. In January 2020, a comprehensive review article was published that demonstrated the effectiveness of natural products as promising anti-HSV drugs. Pyrithione, a zinc ionophore, has shown antiviral activity against herpes simplex. Alzheimer's disease In 1979, it was reported that there is a possible link between HSV-1 and Alzheimer's disease, in people