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 human 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 were divided into seven distinct sub-lineages: BA.1, BA.1.1, BA.2, BA.3, BA.2.12.1, BA.4, and BA.5. As of January 2023, additional new sub-lineages (e.g. BQ.1, BQ.1.1, BF.7, XBB.1, XBB.1.5) have been designated.The Spike (XBB.1.5, Omicron Variant) (SARS-CoV-2) Pseudotyped Lentiviruses were produced with SARS-CoV-2 Spike (Genbank Accession #QHD43416.1 containing all the XBB.1.5 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 (Figure 1), therefore, the spike-mediated cell entry can be measured via luciferase activity. The Spike (XBB.1.5, Omicron Variant) (SARS-CoV-2) pseudovirus can be used to measure the activity of a neutralizing antibody against SARS-CoV-2 Omicron XBB.1.5 variant in a Biosafety Level 2 facility.Figure 1. Schematic of the Luciferase Reporter in SARS-CoV-2 Spike Pseudovirion.As shown in Figure 2, the Spike Omicron XBB.1.5 pseudovirus has been validated for use with ACE2-HEK293 target cells (which overexpress ACE2; BPS Bioscience #79951).Spike Mutations in XBB.1.5 Omicron Variant: T19I, LPP24-26del, A27S, V83A, G142D, Y144del, H146Q, Q183E, V213E, G252V, G339H, R346T, L368I, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, V445P, G446S, N460K, S477N, T478K, E484A, F486P, F490S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K