The pandemic coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). As the first step of the viral replication, the virus attaches to the host cell surface before entering the cell. The viral Spike protein recognizes and attaches to the Angiotensin-Converting Enzyme 2 (ACE2) receptor found on the surface of type I and II pneumocytes, endothelial cells, and ciliated bronchial epithelial cells. Drugs targeting the interaction between the Spike protein of SARS-CoV-2 and ACE2 may offer protection against the viral infection. Omicron Variant was identified in South Africa in November of 2021. This variant has a large number of mutations that allow the virus to spread more easily and quickly than other variants. As of May 2022, Omicron variants have been divided into seven distinct sub-lineages: BA.1, BA.1.1, BA.2, BA.3, BA.2.12.1, BA.4, and BA.5.The Spike (BA.2.12.1, Omicron Variant) (SARS-CoV-2) Pseudotyped Lentiviruses were produced with SARS-CoV-2 Spike (Genbank Accession #QHD43416.1 containing all the Omicron BA.2.12.1 mutations; see below for details) as the envelope glycoprotein instead of the commonly used VSV-G. These pseudovirions contain the firefly luciferase gene driven by a CMV promoter, therefore, the spike-mediated cell entry can be measured via luciferase activity. The Spike (BA.2.12.1, Omicron Variant) (SARS-CoV-2) pseudovirus can be used to measure the activity of a neutralizing antibody against SARS-CoV-2 Omicron BA.2.12.1 variant in a Biosafety Level 2 facility.The Spike Omicron BA.2.12.1 pseudovirus has been validated for use with target cells ACE2-HEK293 (which overexpress ACE2; BPS Bioscience #79951).