Utilizing the Potential of Antimicrobial Peptide LL-37 for Combating SARS-COV- 2 Viral Load in Saliva: an In Silico Analysis.

Limiting the spread of virus during the recent pandemic outbreak was a major challenge. Viral loads in saliva, nasopharyngeal and oropharyngeal swabs were the major cause for droplet transmission and aerosols. Saliva being the major contributor for the presence of viral load is the major key factor; various mouthwashes and their combination were analyzed and utilized in health care centers to hamper the spread of virus and decrease viral load. The compositions of these mouthwashes to an extent affected the viral load and thereby transmission, but there is always a scope for other protocols which may provide better results. Here we evaluated the potential of antimicrobial peptide LL-37 in decreasing the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through an in silico work and evidence from other studies. This narrative review highlighted a brief nonsystematic methodology to include the selected articles for discussion. Accessible electronic databases (Medline, Scopus, Web of Science, SciELO, and PubMed) were used to find studies that reported the salivary viral load of SARS-CoV-2 published between December 2019 and June 2021. The following keywords were utilized for brief searching of the databases: "saliva," "viral load," and "SARS-CoV-2." Articles in English language, in vitro cell-line studies, ex vivo studies, and clinical trials explaining the viral load of SARS-CoV-2 in saliva and strategies to decrease viral load were included in this review. The search was complemented by manual searching of the reference lists of included articles and performing a citation search for any additional reviews. The antiviral potential of cationic host defense peptide LL-37 was evaluated using computational approaches providing in silico evidence. The analysis of docking studies and the display of positive interfacial hydrophobicity of LL-37 resulting in disruption of COVID-19 viral membrane elucidate the fact that LL-37 could be effective against all variants of SARS-CoV-2. Further experimental studies would be needed to confirm the binding of the receptor-binding domain with LL-37. The possibility of using it in many forms further to decrease the viral load by disrupting the viral membrane is seen.

Molecular Insights on the Possible Role of Annexin A2 in COVID-19 Pathogenesis and Post-Infection Complications.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has infected >235 million people and killed over 4.8 million individuals worldwide. Although vaccines have been developed for prophylactic management, there are no clinically proven antivirals to treat the viral infection. Continuous efforts are being made all over the world to develop effective drugs but these are being delayed by periodic outbreak of mutated SARS-CoV-2 and a lack of knowledge of molecular mechanisms underlying viral pathogenesis and post-infection complications. In this regard, the involvement of Annexin A2 (AnxA2), a lipid-raft related phospholipid-binding protein, in SARS-CoV-2 attachment, internalization, and replication has been discussed. In addition to the evidence from published literature, we have performed in silico docking of viral spike glycoprotein and RNA-dependent RNA polymerase with human AnxA2 to find the molecular interactions. Overall, this review provides the molecular insights into a potential role of AnxA2 in the SARS-CoV-2 pathogenesis and post-infection complications, especially thrombosis, cytokine storm, and insulin resistance.

Pathway enrichment analysis of virus-host interactome and prioritization of novel compounds targeting the spike glycoprotein receptor binding domain-human angiotensin-converting enzyme 2 interface to combat SARS-CoV-2.

SARS-CoV-2 has become a pandemic causing a serious global health concern. The absence of effective drugs for treatment of the disease has caused its rapid spread on a global scale. Similarly to the SARS-CoV, the SARS-CoV-2 is also involved in a complex interplay with the host cells. This infection is characterized by a diffused alveolar damage consistent with the Acute Respiratory Disease Syndrome (ARDS). To explore the complex mechanisms of the disease at the system level, we used a network medicine tools approach. The protein-protein interactions (PPIs) between the SARS-CoV and the associated human cell proteins are crucial for the viral pathogenesis. Since the cellular entry of SARS-CoV-2 is accomplished by binding of the spike glycoprotein binding domain (RBD) to the human angiotensin-converting enzyme 2 (hACE2), a molecule that can bind to the spike RDB-hACE2 interface could block the virus entry. Here, we performed a virtual screening of 55 compounds to identify potential molecules that can bind to the spike glycoprotein and spike-ACE2 complex interface. It was found that the compound ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4-piperidine carboxylate (the S54 ligand) and ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4 piperazine carboxylate (the S55 ligand) forms hydrophobic interactions with Tyr41A, Tyr505B and Tyr553B, Leu29A, Phe495B, respectively of the spike glycoprotein, the hotspot residues in the spike glycoprotein RBD-hACE2 binding interface. Furthermore, molecular dynamics simulations and free energy calculations using the MM-GBSA method showed that the S54 ligand is a stronger binder than a known SARS-CoV spike inhibitor SSAA09E3 (N-(9,10-dioxo-9, 10-dihydroanthracen-2-yl) benzamide).Communicated by Ramaswamy H. Sarma.