Phycobilins as Potent Food Bioactive Broad-Spectrum Inhibitors Against Proteases of SARS-CoV-2 and Other Coronaviruses: A Preliminary Study

  1. Brahmaiah Pendyala
  2. Ankit Patras
  3. Chandravanu Dash

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Abstract

In the 21st century, we have witnessed three coronavirus outbreaks: SARS in 2003, MERS in 2012, and the ongoing pandemic coronavirus disease 2019 (COVID-19). The search for efficient vaccines and development and repurposing of therapeutic drugs are the major approaches in the COVID-19 pandemic research area. There are concerns about the evolution of mutant strains (e.g., VUI – 202012/01, a mutant coronavirus in the United Kingdom), which can potentially reduce the impact of the current vaccine and therapeutic drug development trials. One promising approach to counter the mutant strains is the “development of effective broad-spectrum antiviral drugs” against coronaviruses. This study scientifically investigates potent food bioactive broad-spectrum antiviral compounds by targeting main protease (M pro ) and papain-like protease (PL pro ) proteases of coronaviruses (CoVs) using in silico and in vitro approaches. The results reveal that phycocyanobilin (PCB) shows potential inhibitor activity against both proteases. PCB had the best binding affinity to Mpro and PLpro with IC 50 values of 71 and 62 μm, respectively. Also, in silico studies with M pro and PL pro enzymes of other human and animal CoVs indicate broad-spectrum inhibitor activity of the PCB. As with PCB, other phycobilins, such as phycourobilin (PUB), phycoerythrobilin (PEB), and phycoviolobilin (PVB) show similar binding affinity to SARS-CoV-2 M pro and PL pro .

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  1. Version published to 10.3389/fmicb.2021.645713
  2. ScreenIT

    SciScore for 10.1101/2020.11.21.392605: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Due to limitation on availability of crystal PDB structures of PLpro, both dimer and monomeric forms were used in docking studies. For Mpro, docking scores are in the range of −8.3 to −9.3 K.cal/mol. PCB showed higher binding affinity with docking score (−9.3 K.cal/mol) for MERS Mpro followed by HCoV NL63 (−9.0 K.cal/mol) and IBV (−8.9 K.cal/mol). For PLpro, docking scores were in the range of −8.9 to −7.6 K.cal/mol. The results revealed that PCB had higher binding affinity to dimer form of PLpro enzymes than monomeric forms. When compared monomers only, PCB had best docking score for MERS-CoV (−8.5 K.cal/mol) followed by TGEV (−8.1 K.cal/mol) and SARS-CoV-2 (−8.0 K.cal/mol). Figure S2 and S3 show polar contacts of PCB with binding pocket key amino acid residues of Mpro and PLpro enzymes of human and animal CoVs. Surprisingly the docking results suggest PCB as a promising broad-spectrum food bioactive inhibitor compound against CoVs proteases. The computed physical properties of phycocyanobilin show rotatable bond count of 10, hydrogen bond donor count of 5 and hydrogen bond acceptor count of 7 (NCBI, 2020), which makes multiple hydrogen bond interactions between the compound and specific amino acid residues located at the active site of the pocket of the protease enzymes. Molecular docking studies indicated that propionic carboxyl and lactam ring carbonyl oxygens of PCB are involved in polar interactions with aminoacid residues of proteases. 3.4 Inhibitor activities of other...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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  3. Version published to 10.1101/2020.11.21.392605 on bioRxiv