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.1.617.2.1 (also known as the Delta Plus Variant) was identified in India in the spring of 2021. This variant has a number of mutations that increase morbidity and mortality and allow the virus to spread more easily and quickly than other variants.The Spike (B.1.617.2.1 Variant) (SARS-CoV-2) Pseudotyped Lentiviruses were produced with SARS-CoV-2 B.1.617.2.1 Variant Spike (Genbank Accession #QHD43416.1 with B.1.617.2.1 mutations; see below for details) as the envelope glycoproteins instead of the commonly used VSV-G. Compared to the Delta variant (B.1.617.2), variant Delta Plus has an additional mutation, K417N. 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.1.617.2.1 Variant) (SARS-CoV-2) pseudotyped lentivirus can be used to measure the activity of neutralizing antibody against SARS-CoV-2 B.1.617.2.1 variant in a Biosafety Level 2 facility.