The SARS-CoV-2 genome is ~29 kb divided into 10 open reading frames (ORFs). Each of these ORFs (except seemingly ORF10) is translated in 29 different proteins.

ORF1 is formed by two overlapping ORFs, ORF1a and ORF1b, which are cleaved into 16 nonstructural proteins (NSPs).

ORF2 encodes the Spike (S) glycoprotein.

ORF3a and ORF3b encode themselves.

ORF4 encodes the Envelope (E) protein.

ORF5 encodes the Membrane/Matrix (M) protein.

ORF6 encodes itself.

ORF7a and ORF7b are standalone proteins.

ORF8 encodes itself.

ORF9 is formed by three overlapping ORFs; ORF9a encodes the Nucleocapsid (N) protein and ORF9b and ORF9c encode themselves.

ORF10 seems to encode nothing of important at this time.


The Different ORF Proteins

The four structural proteins, S, M, N, and E comprise the matura virion. Sixteen non-structural proteins (NSPs_ and nine of the ten ORF proteins have various functions involved in viral replication, modulating the host cell cycle, and evading the host immune response. Here, we briefly summarize what is known and/or postulated to date regarding the various SARS-CoV-2 ORF proteins:

– ORF3a inhibits autophagy by preventing autolysosome formations. Forms homotetrameric potassium sensitive ion channels. (275 a.a.)

– ORF3b inhibits activation of IFN-I through an unkown mechanism. Generates a strong host immune response. (22 a.a.)

– ORF6 inhibits activation of IFN-I by blocking nuclear translocation of transcription factors. (61 a.a.)

– ORF7a suppresses antigen-presentation in monocytes and after ubiquitination, suppresses STAT2 phosphorylation thereby inhibiting activation of IFN-I. (121 a.a.)

– ORF7b inhibits activation of IFN-I by inhibiting phosphorylation of STAT1 and STAT2. May have leucine zipper functionality. (43 a.a.)

– ORF8 downregulates MHC-I in vitro, inhibiting antigen presentation. Also generates a strong host immune response. (121 a.a.)

– ORF9b inhibits activation of IFN-I by targeting IKK? (NEMO) and TOM70. (97 a.a.)

– ORF9c may interfere with IFN signaling, but it is still being investigated. (73 a.a.)

– ORF10 is not essential for viral replication and variants without this are fully functional. (~38 a.a.)


ProSci’s COVID-19 Research

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