Potential inhibitor for blocking binding between ACE2 and SARS-CoV-2 spike protein with mutations

Area of Science:

• Virology
• Pharmacology
• Traditional Chinese Medicine

Background:

• The COVID-19 pandemic, caused by SARS-CoV-2, has led to millions of deaths globally.
• Numerous SARS-CoV-2 variants have emerged due to high mutation rates, posing ongoing public health challenges.
• Specific mutations in the receptor-binding domain (RBD) of SARS-CoV-2, such as N501Y and E484K, are associated with increased infectivity.

Purpose of the Study:

• To investigate the potential of a herbal compound, GB-1, in inhibiting the interaction between SARS-CoV-2 variants and the human ACE2 receptor.
• To evaluate the efficacy of GB-1 against various SARS-CoV-2 mutations, including combined and single mutations.

Main Methods:

• In vitro assays were performed to assess the inhibitory activity of GB-1 against the binding of SARS-CoV-2 RBD to ACE2.
• The study examined GB-1's effect on the Wuhan strain and specific mutant variants (K417N-E484K-N501Y, L452R-T478K, E484K, N501Y, and K417N).
• The inhibitory role of glycyrrhizic acid, a component of GB-1, was also analyzed.

Main Results:

• GB-1 demonstrated significant inhibition of ACE2-RBD binding for the Wuhan strain and key variants like K417N-E484K-N501Y and L452R-T478K.
• GB-1 also inhibited binding with single mutations E484K and N501Y, but not K417N.
• Glycyrrhizic acid inhibited binding with the Wuhan strain but not the K417N-E484K-N501Y triple mutant.

Conclusions:

• GB-1 shows promise as a potential prophylactic agent against diverse SARS-CoV-2 variants.
• The compound's ability to inhibit ACE2-RBD binding across multiple mutations underscores its therapeutic potential for COVID-19.
• Further research into GB-1 and its components could lead to novel strategies for combating SARS-CoV-2 infections.