I keep coming across the term "polybasic cleavage site" which is implicated in increasing the virulence of many viruses, but I'm struggling to find a definition. Is it just a sequence of amino acids where more than one has a basic side chain? I'd also love to know why it is so important to the function of a virus.


2 Answers 2


I would define a “polybasic cleavage site” as:

A region on a protein consisting of several basic amino acids (generally arginine (R) and lysine (K), rather than histidine) that determines the substrate specificity of certain classes of proteases for that protein.

It can also be regarded as a recognition site for the enzyme.

The relevance of this to the virulence of some viruses is as follows. Many RNA viruses are translated into one or more polyproteins that are subsequently cleaved proteolytically at specific sites to generate further proteins. In certain instances these sites are ‘polybasic’, and the products generated by the cleavage of such sites play a role in the virulence of viruses.

This is nicely illustrated by a paper by Nao et al. in mBio on the mutation of haemagglutinin (HA) cleavage site of Avian Influenza Virus, where increasing the number of basic amino acids increased the virulence. I included an illustrative figure from that publication.

HA cleavage site sequences

HA cleavage site sequences of the ShimH5 virus strain and its variants passaged in chickens

The current (2021) interest in polybasic cleavage sites no doubt relates to the presence of such a site (PRRAR) at the S1/S2 junction in the spike protein of SARS-CoV-2 — see, for example, this paper by Peacock et al. in Nature Microbiology.


A polybasic cleavage site is a cleavage site consisting of polybasic amino acids. An acid is polybasic when it is able to donate more than one proton in aqueous solution. In a titration curve, polybasic acids show as many equivalence points as they are poly. https://www.w3spoint.com/ionization-of-a-polybasic-acid

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    $\begingroup$ Unfortunately, your logical analysis of the word — a site with a single acidic amino acid residue with multiple ionizations — is incorrect because no such amino acids exist in proteins, and, as I indicated in my comment on the question, the usage is for a site with many basic amino acid residues. $\endgroup$
    – David
    Jul 9, 2021 at 16:08
  • $\begingroup$ You are right thank you for pointing this out $\endgroup$ Jul 10, 2021 at 9:08

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