Inactivated SARS-CoV-2 Variant Omicron, Lineage BA.4.6 (USA/MD-HP35538/2022)

Coronaviruses (family Coronaviridae) are common pathogens of humans and animals. Four coronaviruses are prevalent in humans (human coronavirus NL63 (HCoV-NL63), HCoV-229E, HCoV-OC43, and HCoV-HKU1), typically infecting the upper respiratory tract and causing common cold symptoms. Over the past two decades, three zoonotic coronaviruses (severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2) have infected humans after spillover from animal reservoirs. These three viruses can replicate in the lower respiratory tract and can cause potentially fatal acute respiratory distress syndrome (ARDS).

SARS-CoV-2 shares 79% sequence similarity with SARS-CoV and belongs to the genus Sarbecovirus. The virus encodes a set of structural proteins (membrane, nucleocapsid, envelope, and spike glycoprotein), nonstructural proteins (most of which are part of the viral replication and transcription complex), and accessory proteins. Structural proteins, together with the host''s lipid bilayer, form the enveloped virion (or viral particle), which transports the viral genomic RNA into the cell. Accessory proteins are not essential for replication but often have immune evasion activities. The primary determinant of coronavirus tropism is the spike glycoprotein, which forms a trimer on the viral surface. The spike protein consists of two subunits: the S1 subunit, which binds to the host entry receptor angiotensin-converting enzyme 2 (ACE2), and the S2 subunit, which mediates membrane fusion. These two subunits are separated by the S1-S2 site, which contains a furin cleavage motif and is cleaved in virus-producing cells. After binding to ACE2 on target cells, the spike protein is cleaved at the S2'' site by the transmembrane serine protease TMPRSS2. This cleavage activates the S2 subunit trimer, allowing fusion of the viral and host lipid bilayer membranes and releasing the viral ribonucleoprotein complex into the cell.