AnnCovDB: a manually curated annotation database for mutations in SARS-CoV-2 spike protein.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been circulating and adapting within the human population for >4 years. A large number of mutations have occurred in the viral genome, resulting in significant variants known as variants of concern (VOCs) and variants of interest (VOIs). The spike (S) protein harbors many of the characteristic mutations of VOCs and VOIs, and significant efforts have been made to explore functional effects of the mutations in the S protein, which can cause or contribute to viral infection, transmission, immune evasion, pathogenicity, and illness severity. However, the knowledge and understanding are dispersed throughout various publications, and there is a lack of a well-structured database for functional annotation that is based on manual curation. AnnCovDB is a database that provides manually curated functional annotations for mutations in the S protein of SARS-CoV-2. Mutations in the S protein carried by at least 8000 variants in the GISAID were chosen, and the mutations were then utilized as query keywords to search in the PubMed database. The searched publications revealed that 2093 annotation entities for 205 single mutations and 93 multiple mutations were manually curated. These entities were organized into multilevel hierarchical categories for user convenience. For example, one annotation entity of N501Y mutation was 'Infectious cycle➔Attachment➔ACE2 binding affinity➔Increase'. AnnCovDB can be used to query specific mutations and browse through function annotation entities. Database URL: https://AnnCovDB.app.bio-it.tech/.