The pathogen SARS-CoV2 is extremely infectious. The novel SARS-CoV2 (2019-nCoV) virus that causes COVID-19 is resistant to the current antiviral medications, leading to an extremely high fatality rate. Millions of people have been affected by COVID-19 worldwide, and the number is dangerously rising due to the ongoing rise in cases. Toward developing SARS-COV-2 inhibitors, many pyrimidine and purine analogs have been depicted. Thus in order to developing new purine analogs the synthetic approach to prepare methylsulfanylpyrimidine nuclei is accomplished. Successful generation of a new series of triazolopyrimidines (TZP) as a new bio-isostere purine analog is furnished under mild conditions with high yields in a different manner from the traditional approaches and avoided the sophisticated methods. The crossponding triazolopyrazolopyrimidines which are characterized by the presence of tri-fused heterocyclic ring system were also produced. Selected compounds were tested for inhibition of SARS-CoV-2 viral replication. The antiproliferative efficacy of the newly synthesized compounds was also examined on a panel of NCI 60 human cancer cell lines. Our results demonstrated that the triazolopyrimidines 9b is a very promising novel purine analog that focus and highlights the potential of the TPZ scaffold as anti-CoV agent and is worthy of further evaluation as a potential therapeutic agent.