Alkamides and Piperamides as Potential Antivirals against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

The pandemic caused by
the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has
quickly spread globally, infecting millions and killing hundreds of
thousands of people. Herein, to identify potential antiviral agents,
97 natural amide-like compounds known as alkamides and piperamides
were tested against SARS-CoV-2 main protease (Mpro) and RNA-dependent
RNA polymerase (RdRp), and the human angiotensin-converting enzyme
2 (ACE2) using molecular docking and molecular dynamics simulations.
The docking results showed that alkamides and dimeric piperamides
from Piper species have a high binding affinity and
potential antiviral activity against SARS-CoV-2. The absorption, distribution,
metabolism, and excretion (ADME) profile and Lipinski’s rule
of five showed that dimeric piperamides have druglikeness potential.
The molecular dynamics results showed that pipercyclobutanamide B
forms a complex with Mpro at a similar level of stability than N3-I.
Our overall results indicate that alkamides and piperamides, and specifically
pipercyclobutanamide B, should be further studied as compounds with
SARS-CoV-2 antiviral properties.