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

At the time of writing, more than 440 million confirmed coronavirus disease 2019 (COVID-19) cases and more than 5.97 million COVID-19 deaths worldwide have been reported by the World Health Organization since the start of the outbreak of the pandemic in Wuhan, China. During the COVID-19 pandemic, many variants of SARS-CoV-2 have arisen because of high mutation rates. N501Y, E484K, K417N, K417T, L452R and T478K in the receptor binding domain (RBD) region may increase the infectivity in several variants of SARS-CoV-2. In this study, we discovered that GB-1, developed from Chiehyuan herbal formula which obtained from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and RBD with Wuhan type, K417N-E484K-N501Y and L452R-T478K mutation. In addition, GB-1 inhibited the binding between ACE2 and RBD with a single mutation (E484K or N501Y), except the K417N mutation. In the compositions of GB-1, glycyrrhizic acid can inhibit the binding between ACE2 and RBD with Wuhan type, except K417N-E484K-N501Y mutation. Our results suggest that GB-1 could be a potential candidate for the prophylaxis of different variants of SARS-CoV-2 infection because of its inhibition of binding between ACE2 and RBD with different mutations (L452R-T478K, K417N-E484K-N501Y, N501Y or E484K).

A Hybrid Recommendation Approach for Viral Food Based on Online Reviews.

Nowadays, there are many types of viral foods and consumers expect to be able to quickly find foods that meet their own tastes. Traditional recommendation systems make recommendations based on the popularity of viral foods or user ratings. However, because of the different sentimental levels of users, deviations occur and it is difficult to meet the user's specific needs. Based on the characteristics of viral food, this paper constructs a hybrid recommendation approach based on viral food reviews and label attribute data. A user-based recommendation approach is combined with a content-based recommendation approach in a weighted combination. Compared with the traditional recommendation approaches, it is found that the hybrid recommendation approach performs more accurately in identifying the sentiments of user evaluations, and takes into account the similarities between users and foods. We can conclude that the proposed hybrid recommendation approach combined with the sentimental value of food reviews provides novel insights into improving the existing recommendation system used by e-commerce platforms.

GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2.

Since the start of the outbreak of coronavirus disease 2019 in Wuhan, China, there have been more than 150 million confirmed cases of the disease reported to the World Health Organization. The beta variant (B.1.351 lineage), the mutation lineages of SARS-CoV-2, had increase transmissibility and resistance to neutralizing antibodies due to multiple mutations in the spike protein. N501Y, K417N and E484K, in the receptor binding domain (RBD) region may induce a conformational change of the spike protein and subsequently increase the infectivity of the beta variant. The L452R mutation in the epsilon variant (the B.1.427/B.1.429 variants) also reduced neutralizing activity of monoclonal antibodies. In this study, we discovered that 300 µg/mL GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and wild-type (Wuhan type) RBD spike protein. GB-2 can inhibit the binding between ACE2 and RBD with K417N-E484K-N501Y mutation in a dose-dependent manner. GB-2 inhibited the binding between ACE2 and the RBD with a single mutation (K417N or N501Y or L452R) except the E484K mutation. In the compositions of GB-2, glycyrrhiza uralensis Fisch. ex DC., theaflavin and (+)-catechin cannot inhibit the binding between ACE2 and wild-type RBD spike protein. Theaflavin 3-gallate can inhibit the binding between ACE2 and wild-type RBD spike protein. Our results suggest that GB-2 could be a potential candidate for the prophylaxis of some SARS-CoV-2 variants infection in the further clinical study because of its inhibition of binding between ACE2 and RBD with K417N-E484K-N501Y mutations or L452R mutation.

The potential SARS-CoV-2 entry inhibitor (preprint)

Outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan and has rapidly spread to almost all parts of world. In coronaviruses, the receptor binding domain (RBD) in the distal part of S1 subunit of SARS-CoV-2 spike protein can directly bind to angiotensin converting enzyme 2 (ACE2). RBD promote viral entry into the host cells and is an important therapeutic target. In this study, we discovered that theaflavin showed the lower idock score (idock score: -7.95 kcal/mol). To confirm the result, we discovered that theaflavin showed FullFitness score of -991.21 kcal/mol and estimated {Delta}G of -8.53 kcal/mol for the most favorable interaction with contact area of SARS-CoV-2 RBD by SwissDock service. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were formed between theaflavin and Arg454, Phe456, Asn460, Cys480, Gln493, Asn501 and Val503 of SARS-CoV-2 RBD, near the direct contact area with ACE2. Our results suggest that theaflavin could be the candidate of SARS-CoV-2 entry inhibitor for further study.