Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag

Abstract

We are currently witnessing a major epidemic caused by the 2019 novel coronavirus (2019-nCoV). The evolution of 2019-nCoV remains elusive. We found 4 insertions in the spike glycoprotein (S) which are unique to the 2019-nCoV and are not present in other coronaviruses. Importantly, amino acid residues in all the 4 inserts have identity or similarity to those in the HIV-1 gp120 or HIV-1 Gag. Interestingly, despite the inserts being discontinuous on the primary amino acid sequence, 3D-modelling of the 2019-nCoV suggests that they converge to constitute the receptor binding site. The finding of 4 unique inserts in the 2019-nCoV, all of which have identity /similarity to amino acid residues in key structural proteins of HIV-1 is unlikely to be fortuitous in nature. This work provides yet unknown insights on 2019-nCoV and sheds light on the evolution and pathogenicity of this virus with important implications for diagnosis of this virus.

HIV-1 did not contribute to the 2019-nCoV genome

“…The detection of completely matched sequences of 1 and 2 insertions in only a few HIV-1 strains demonstrated that four insertions are very rare or not present among tens of thousands of natural HIV-1 sequences. This also explains why four insertion homolog sequences could only be independently found in different HIV-1 genomes [8]. Because of their poor .…”

“…This insertion is located too far to be considered to form the same structural unit with the other three insertions in the 2019-nCoV spike protein ( Figure 1C). We do not see any selection benefit or rationale for 2019-nCoV to obtain and mix structurally unrelated parts of HIV-1 to generate a unique structure for its enhanced receptor binding as indicated by the authors [8].…”

“…identities to and rareness in the HIV-1 sequences, HIV-1 could not be the source for those insertion sequences in the 2019-nCoV genome. Second, these insertions are present not only in 2019-nCoV viruses but also in three betaCoV sequences from bats: two (ZC45 and ZXC21) from Zhejiang deposited in GenBank in 2018 and RaTG13 from Yunnan obtained in 2013 [8]. The RaTG13 is much more similar to 2019-nCoV than both ZC45 and ZXC21 ( Figure 1A).…”

“…This notion has been fully debunked in the media. A recent informally presented report, however, showed that 2019-nCoV had four insertions in the spike glycoprotein gene that is critical for the virus to enter the target cells when compared to other coronaviruses [8]. It was claimed that these inserts were either identical or similar to the motifs in the highly variable (V) regions (V1, V4 and V5) in the envelope glycoprotein or in the Gag protein of some unique HIV-1 strains from three different countries (Thailand, Kenya and India).…”

Early in the epidemic: impact of preprints on global discourse about COVID-19 transmissibility

“…This particular drawback has been highlighted during the ongoing outbreak, especially after the high-profile withdrawal of a virology study from the preprint server bioRxiv, which erroneously claimed that COVID-19 contained HIV "insertions". 21 The very fact that this study was withdrawn showcases the power of open peer-review during emergencies; the withdrawal itself appears to have been prompted by outcry from dozens of scientists from around the globe who had access to the study because it was placed on a public server. 22 Much of this outcry was documented on Twitter (a microblogging platform) and on longer-form popular science blogs, signalling that such fora would serve as rich additional data sources for future work on the impact of preprints on public discourse.…”