The pandemic coronavirus disease 2019 () 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. A variant called B.1.1.529 BA.1 (also known as the 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. A sub-lineage of BA.1 with an R346K substitution in the spike protein is classified as B.1.1.529 BA.1.1.The Spike (B.1.1.529 BA.1.1, Omicron Variant R346K) (SARS-CoV-2) Pseudotyped Lentiviruses were produced with SARS-CoV-2 B.1.1.529 BA.1.1 Variant Spike (Genbank Accession #QHD43416.1 with B.1.1.529 BA.1.1 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 (B.1.1.529 BA.1.1, Omicron Variant R346K Variant) (SARS-CoV-2) pseudovirus can be used to measure the activity of a neutralizing antibody against SARS-CoV-2 B.1.1.529 BA.1.1 variant in a Biosafety Level 2 facility.The Spike B.1.1.529 BA.1.1 pseudovirus has been validated for use with target cells ACE2-HEK293 (which overexpress ACE2; BPS Bioscience #79951).Spike Mutations in B.1.1.529 BA.1.1 Omicron Variant R346K:A67V, Δ69-70, T95I, G142D, Δ143-145, Δ211, L212I, ins214EPE, G339D, R346K, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F