<p>Background:
Accessing COVID-19 vaccines is a challenge despite successful clinical trials.
This burdens the COVID-19 treatment gap, thereby requiring accelerated
discovery of anti-SARS-CoV-2 agents. Thus, this study explored the potential of
anti-HIV reverse transcriptase (RT) phytochemicals as inhibitors of SARS-CoV-2
non-structural proteins (nsps) by targeting <i>in
silico</i> key sites in the structures of SARS-CoV-2 nsps. Moreover, structures
of the anti-HIV compounds were considered for druggability and toxicity. 104
anti-HIV phytochemicals were subjected to molecular docking with papain-like
protease (nsp3), 3-chymotrypsin-like protease (nsp5), RNA-dependent RNA
polymerase (nsp12), helicase (nsp13), SAM-dependent 2’-<i>O-</i>methyltransferase (nsp16) and its cofactor (nsp10), and
endoribonuclease (nsp15). Drug-likeness and ADME (absorption, distribution,
metabolism, and excretion) properties of the top ten compounds per nsp were
predicted using SwissADME. Their toxicity was also determined using OSIRIS
Property Explorer.</p>
<p>Results:
Among the twenty-seven top-scoring compounds, the polyphenolic natural products
amentoflavone (<b>1</b>), robustaflavone (<b>4</b>), punicalin (<b>9</b>), volkensiflavone (<b>11</b>),
rhusflavanone (<b>13</b>), morelloflavone (<b>14</b>), hinokiflavone (<b>15</b>), and michellamine B (<b>19</b>) were multi-targeting and had the
strongest affinities to at least two of the nsps (Binding Energy = -7.7 to
-10.8 kcal/mol). Friedelin (<b>2</b>),
pomolic acid (<b>5</b>), ursolic acid (<b>10</b>), garcisaterpenes A (<b>12</b>), hinokiflavone (<b>15</b>), and digitoxigenin-3-<i>O-</i>glucoside (<b>17</b>) were computationally druggable. Moreover, compounds <b>5</b> and <b>17</b> showed good gastrointestinal absorptive property. Most of the
compounds were also predicted to be non-toxic.</p>
<p>Conclusions:
Twenty anti-HIV RT phytochemicals showed multi-targeting inhibitory potential
against SARS-CoV-2 nsp3, 5, 10, 12, 13, 15, and 16, and can therefore be used
as prototypes for anti-COVID-19 drug design.</p>
In-silico designing of acyclic nucleoside phosphonates and their anti-HIV potential
