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

Figure 3. Modelled homo-trimer spike glycoprotein of 2019-nCoV virus. The inserts from HIV envelop protein are shown with colored beads, present at the binding site of the protein. — **Figure 3. Modelled homo-trimer spike glycoprotein of 2019-nCoV virus. The inserts from HIV**
**envelop protein are shown with colored beads, present at the binding site of the protein.**

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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.

Insertions share similarity to HIV
The insertions were observed to be present in all the genomic sequences of 2019-nCoV virus
available from the recent clinical isolates (Supplementary Figure 1). To know the source of these
insertions in 2019-nCoV a local alignment was done with BLASTp using these insertions as query
with all virus genome. Unexpectedly, all the insertions got aligned with Human immunodeficiency
Virus-1 (HIV-1). Further analysis revealed that aligned sequences of HIV-1 with 2019-nCoV were
derived from surface glycoprotein gp120 (amino acid sequence positions: 404-409, 462-467, 136-
150) and from Gag protein (366-384 amino acid) (Table 1). Gag protein of HIV is involved in host
membrane binding, packaging of the virus and for the formation of virus-like particles. Gp120
plays crucial role in recognizing the host cell by binding to the primary receptor CD4.This binding
induces structural rearrangements in GP120, creating a high affinity binding site for a chemokine
co-receptor like CXCR4 and/or CCR5.

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

Conclusions
Our analysis of the spike glycoprotein of 2019-nCoV revealed several interesting findings: First,
we identified 4 unique inserts in the 2019-nCoV spike glycoprotein that are not present in any
other coronavirus reported till date. To our surprise, all the 4 inserts in the 2019-nCoV mapped to short segments of amino acids in the HIV-1 gp120 and Gag among all annotated virus proteins in
the NCBI database. This uncanny similarity of novel inserts in the 2019- nCoV spike protein to
HIV-1 gp120 and Gag is unlikely to be fortuitous. Further, 3D modelling suggests that atleast 3 of
the unique inserts which are non-contiguous in the primary protein sequence of the 2019-nCoV
spike glycoprotein converge to constitute the key components of the receptor binding site. Of note,
all the 4 inserts have pI values of around 10 that may facilitate virus-host interactions. Taken
together, our findings suggest unconventional evolution of 2019-nCoV that warrants further
investigation. Our work highlights novel evolutionary aspects of the 2019-nCoV and has
implications on the pathogenesis and diagnosis of this virus.