Vaccines against the SARS-CoV-2 virus are just becoming available. While this is good news for controlling the spread of the virus, there has not been as much success in developing therapeutic agents for treating patients infected with SARS-CoV-2.  A significant amount of research is being published on laboratory studies and computer modeling to find peptides that may have potential therapeutic or diagnostic applications.  Below are some of the recently published papers concerning SARS-CoV-2.

Conserved High Free Energy Sites in Human Coronavirus Spike Glycoprotein Backbones

Robert C Penner , J Comput Biol, 2020 Nov;27(11):1622-1630.

doi: 10.1089/cmb.2020.0193. Epub 2020 May 13.

Methods previously developed by the author are applied to uncover several sites of interest in the spike glycoproteins of all known human coronaviruses (hCoVs), including SARS-CoV-2 that causes COVID-19. The sites comprise three-dimensional neighborhoods of peptides characterized by four key properties: (1) they pinpoint regions of high free energy in the backbone whose obstruction might interrupt function; (2) by their very definition, they occur rarely in the universe of all gene-encoded proteins that could obviate host response to compounds designed for their interference; (3) they are common to all known hCoV spikes, possibly retaining activity in light of inevitable viral mutation; and (4) they are exposed in the molecular surface of the glycoprotein. These peptides in SARS-CoV-2 are given by the triples of residues (131, 117, 134), (203, 227, 228), and (1058, 730, 731) in its spike.

Neuropilin-1 is a host factor for SARS-CoV-2 infection

James L Daly, Boris Simonetti, Katja Klein, Kai-En Chen, Maia Kavanagh Williamson, Carlos Antón-Plágaro, Deborah K Shoemark, Lorena Simón-Gracia, Michael Bauer, Reka Hollandi, Urs F Greber, Peter Horvath, Richard B Sessions, Ari Helenius, Julian A Hiscox, Tambet Teesalu, David A Matthews, Andrew D Davidson, Brett M Collins, Peter J Cullen, Yohei Yamauchi, Science. 2020 Nov 13;370(6518):861-865.

doi: 10.1126/science.abd3072. Epub 2020 Oct 20.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), uses the viral spike (S) protein for host cell attachment and entry. The host protease furin cleaves the full-length precursor S glycoprotein into two associated polypeptides: S1 and S2. Cleavage of S generates a polybasic Arg-Arg-Ala-Arg carboxyl-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface neuropilin-1 (NRP1) and NRP2 receptors. We used x-ray crystallography and biochemical approaches to show that the S1 CendR motif directly bound NRP1. Blocking this interaction by RNA interference or selective inhibitors reduced SARS-CoV-2 entry and infectivity in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19.

Peptide and peptide-based inhibitors of SARS-CoV-2 entry

Desiree Schütz, Yasser B Ruiz-Blanco, Jan Münch, Frank Kirchhoff , Elsa Sanchez-Garcia, Janis A Müller, Adv Drug Deliv Rev. 2020 Nov 13;167:47-65.

doi: 10.1016/j.addr.2020.11.007.Online ahead of print.

Abstract

To date, no effective vaccines or therapies are available against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pandemic agent of the coronavirus disease 2019 (COVID-19). Due to their safety, efficacy and specificity, peptide inhibitors hold great promise for the treatment of newly emerging viral pathogens. Based on the known structures of viral proteins and their cellular targets, antiviral peptides can be rationally designed and optimized. The resulting peptides may be highly specific for their respective targets and particular viral pathogens or exert broad antiviral activity. Here, we summarize the current status of peptides inhibiting SARS-CoV-2 entry and outline the strategies used to design peptides targeting the ACE2 receptor or the viral Spike protein and its activating proteases furin, transmembrane serine protease 2 (TMPRSS2), or cathepsin L. In addition, we present approaches used against related viruses such as SARS-CoV-1 that might be implemented for inhibition of SARS-CoV-2 infection.

Highly conserved binding region of ACE2 as a receptor for SARS-CoV-2 between humans and mammals

Takuma Hayashi, Kaoru Abiko, Masaki Mandai, Nobuo Yaegashi, Ikuo Konishi, Vet Q. 2020 Dec;40(1):243-249.

doi: 10.1080/01652176.2020.1823522.

Abstract

Several cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection transmitted from human owners to their dogs have recently been reported. The first ever case of SARS-CoV-2 transmission from a human owner to a domestic cat was confirmed on March 27, 2020. A tiger from a zoo in New York, USA, was also reportedly infected with SARS-CoV-2. It is believed that SARS-CoV-2 was transmitted to tigers from their caretakers, who were previously infected with this virus. On May 25, 2020, the Dutch Minister of Agriculture, Nature and Food Quality reported that two employees were infected with SARS-CoV-2 transmitted from minks. These reports have influenced us to perform a comparative analysis among angiotensin-converting enzyme 2 (ACE2) homologous proteins for verifying the conservation of specific protein regions. One of the most conserved peptides is represented by the peptide “353-KGDFR-357 (H. sapiens ACE2 residue numbering), which is located on the surface of the ACE2 molecule and participates in the binding of SARS-CoV-2 spike receptor binding domain (RBD). Multiple sequence alignments of the ACE2 proteins by ClustalW, whereas the three-dimensional structure of its binding region for the spike glycoprotein of SARS-CoV-2 was assessed by means of Spanner, a structural homology modeling pipeline method. In addition, evolutionary phylogenetic tree analysis by ETE3 was used. ACE2 works as a receptor for the SARS-CoV-2 spike glycoprotein between humans, dogs, cats, tigers, minks, and other animals, except for snakes. The three-dimensional structure of the KGDFR hosting protein region involved in direct interactions with SARS-CoV-2 spike RBD of the mink ACE2 appears to form a loop structurally related to the human ACE2 corresponding protein loop, despite of the reduced available protein length (401 residues of the mink ACE2 available sequence vs 805 residues of the human ACE2). The multiple sequence alignments of the ACE2 proteins shows high homology and complete conservation of the five amino acid residues: 353-KGDFR-357 with humans, dogs, cats, tigers, minks, and other animals, except for snakes. Where the information revealed from our examinations can support precision vaccine design and the discovery of antiviral therapeutics, which will accelerate the development of medical countermeasures, the World Health Organization recently reported on the possible risks of reciprocal infections regarding SARS-CoV-2 transmission from animals to humans.

Peptide modelling and screening against human ACE2 and spike glycoprotein RBD of SARS-CoV-2

Shravan B Rathod, Pravin B Prajapati, Lata B Punjabi, Kuntal N Prajapati, Neha Chauhan, Mohmedyasin F Mansuri,  In Silico Pharmacol. 2020 Nov 9;8(1):3.

doi: 10.1007/s40203-020-00055-w. eCollection 2020.

Abstract

Outbreak of Coronavirus Disease 2019 (COVID-19) has become a great challenge for scientific community globally. Virus enters cell through spike glycoprotein fusion with ACE2 (Angiotensin-Converting Enzyme 2) human receptor. Hence, spike glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a potential target for diagnostics, vaccines, and antibodies. Also, virus entry can be prevented by blocking ACE2 thus, ACE2 can be considered potential target for therapeutics. As being highly specific, safe and efficacious, peptides hold their place in therapeutics. In present study, we retrieved sequence of 70 peptides from Antiviral Peptide Database (AVPdb), modelled them using 3D structure predicting web tool and docked them with receptor binding domain (RBD) of spike protein and human host receptor ACE2 using peptide-protein docking. It was observed that peptides have more affinity towards ACE2 in comparison with spike RBD. Interestingly it was noticed that most of the peptides bind to RBM (residue binding motif) which is responsible for ACE2 binding at the interface of RBD while, for ACE2, peptides prefer to bind the core cavity rather than RBD binding interface. To further investigate how peptides at the interface of RBD or ACE2 alter the binding between RBD and ACE2, protein-protein docking of RBD and ACE2 with and without peptides was performed. Peptides, AVP0671 at RBD and AVP1244 at ACE2 interfaces significantly reduce the binding affinity and change the orientation of RBD and ACE2 binding. This finding suggests that peptides can be used as a drug to inhibit virus entry in cells to stop COVID-19 pandemic in the future after experimental evidences.

Computational Design of 25-mer Peptide Binders of SARS-CoV-2

Thassanai Sitthiyotha, Surasak Chunsrivirot, J Phys Chem B. 2020 Dec 3;124(48):10930-10942.

doi: 10.1021/acs.jpcb.0c07890. Epub 2020 Nov 17.

Abstract

SARS-CoV-2 is the novel coronavirus causing the COVID-19 pandemic. To enter human cells, the receptor-binding domain (RBD) of the S1 subunit of SARS-CoV-2 (SARS-CoV-2-RBD) initially binds to the peptidase domain of angiotensin-converting enzyme 2 receptor (ACE2-PD). Using peptides to inhibit SARS-CoV-2-RBD binding to ACE2 is a potential therapeutic solution for COVID-19. A previous study identified a 23-mer peptide (SBP1) that bound to SARS-CoV-2-RBD with comparable K_D to ACE2. We employed computational protein design and molecular dynamics (MD) to design SARS-CoV-2-RBD 25-mer peptide binders (SPB25) with better predicted binding affinity than SBP1. Using residues 21-45 of the α1 helix of ACE2-PD as the template, our strategy is employing Rosetta to enhance SPB25 binding affinity to SARS-CoV-2-RBD and avoid disrupting existing favorable interactions by using residues that have not been reported to form favorable interactions with SARS-CoV-2-RBD as designed positions. Designed peptides with better predicted binding affinities, by Rosetta, than SPB25 were subjected to MD validation. The MD results show that five designed peptides (SPB25_F8N, SPB25_F8R, SPB25_L25R, SPB25_F8N/L25R, and SPB25_F8R/L25R) have better predicted binding affinities, by the MM-GBSA method, than SPB25 and SBP1. This study developed an approach to design SARS-CoV-2-RBD peptide binders, and these peptides may be promising candidates as potential SARS-CoV-2 inhibitors.

Design of an epitope-based peptide vaccine against the SARS-CoV-2: a vaccine-informatics approach

Aftab Alam, Arbaaz Khan, Nikhat Imam, Mohd Faizan Siddiqui, Mohd Waseem, Md Zubbair Malik, Romana Ishrat, Brief Bioinform. 2020 Dec 8;bbaa340.

doi: 10.1093/bib/bbaa340. Online ahead of print.

Abstract

The recurrent and recent global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has turned into a global concern which has infected more than 42 million people all over the globe, and this number is increasing in hours. Unfortunately, no vaccine or specific treatment is available, which makes it more deadly. A vaccine-informatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides [including thymus cells (T-cells) and bone marrow or bursa-derived cells] in the surface glycoprotein (SG) of SARS-CoV-2 which is nontoxic and nonallergenic in nature, nonallergenic, highly antigenic and non-mutated in other SARS-CoV-2 virus strains. The population coverage analysis has found that cluster of differentiation 4 (CD4+) T-cell peptides showed higher cumulative population coverage over cluster of differentiation 8 (CD8+) peptides in the 16 different geographical regions of the world. We identified 12 peptides ((LTDEMIAQY, WTAGAAAYY, WMESEFRVY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQI, YGFQPTNGVGYQ, LPDPSKPSKR, QTQTNSPRRARS and VITPGTNTSN) that are $80hbox{–} 90%$ identical with experimentally determined epitopes of SARS-CoV, and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that the identified peptides are tightly bound in the groove of human leukocyte antigen molecules which can induce the T-cell response. Overall, this study allows us to determine potent peptide antigen targets in the SG on intuitive grounds, which opens up a new horizon in the coronavirus disease (COVID-19) research. However, this study needs experimental validation by in vitro and in vivo.

Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions

Pranam Chatterjee, Manvitha Ponnapati, Christian Kramme, Alexandru M Plesa, George M Church, Joseph M Jacobson, Commun Biol. 2020 Nov 23;3(1):715.

doi: 10.1038/s42003-020-01470-7.

Abstract

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has elicited a global health crisis of catastrophic proportions. With only a few vaccines approved for early or limited use, there is a critical need for effective antiviral strategies. In this study, we report a unique antiviral platform, through computational design of ACE2-derived peptides which both target the viral spike protein receptor binding domain (RBD) and recruit E3 ubiquitin ligases for subsequent intracellular degradation of SARS-CoV-2 in the proteasome. Our engineered peptide fusions demonstrate robust RBD degradation capabilities in human cells and are capable of inhibiting infection-competent viral production, thus prompting their further experimental characterization and therapeutic development.

In Silico Discovery of Antimicrobial Peptides as an Alternative to Control SARS-CoV-2

Yamil Liscano, Jose Oñate-Garzón, Iván Darío Ocampo-Ibáñez, Molecules. 2020 Nov 25;25(23):E5535.

doi: 10.3390/molecules25235535.

Abstract

A serious pandemic has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The interaction between spike surface viral protein (Sgp) and the angiotensin-converting enzyme 2 (ACE2) cellular receptor is essential to understand the SARS-CoV-2 infectivity and pathogenicity. Currently, no drugs are available to treat the infection caused by this coronavirus and the use of antimicrobial peptides (AMPs) may be a promising alternative therapeutic strategy to control SARS-CoV-2. In this study, we investigated the in silico interaction of AMPs with viral structural proteins and host cell receptors. We screened the antimicrobial peptide database (APD3) and selected 15 peptides based on their physicochemical and antiviral properties. The interactions of AMPs with Sgp and ACE2 were performed by docking analysis. The results revealed that two amphibian AMPs, caerin 1.6 and caerin 1.10, had the highest affinity for Sgp proteins while interaction with the ACE2 receptor was reduced. The effective AMPs interacted particularly with Arg995 located in the S2 subunits of Sgp, which is key subunit that plays an essential role in viral fusion and entry into the host cell through ACE2. Given these computational findings, new potentially effective AMPs with antiviral properties for SARS-CoV-2 were identified, but they need experimental validation for their therapeutic effectiveness.

Targeting the SARS-CoV-2 main protease using FDA-approved Isavuconazonium, a P2-P3 α-ketoamide derivative and Pentagastrin: An in-silico drug discovery approach

Ikechukwu Achilonu, Emmanuel Amarachi Iwuchukwu, Okechinyere Juliet Achilonu, Manuel Antonio Fernandes, Yasien Sayed, J Mol Graph Model. 2020 Dec;101:107730.

doi: 10.1016/j.jmgm.2020.107730. Epub 2020 Sep 2.

Abstract

The SARS-CoV-2 main protease (M^pro) is an attractive target towards discovery of drugs to treat COVID-19 because of its key role in virus replication. The atomic structure of M^pro in complex with an α-ketoamide inhibitor (Lig13b) is available (PDB ID:6Y2G). Using 6Y2G and the prior knowledge that protease inhibitors could eradicate COVID-19, we designed a computational study aimed at identifying FDA-approved drugs that could interact with M^pro. We searched the DrugBank and PubChem for analogs and built a virtual library containing ∼33,000 conformers. Using high-throughput virtual screening and ligand docking, we identified Isavuconazonium, a ketoamide inhibitor (α-KI) and Pentagastrin as the top three molecules (Lig13b as the benchmark) based on docking energy. The ΔG_bind of Lig13b, Isavuconazonium, α-KI, Pentagastrin was -28.1, -45.7, -44.7, -34.8 kcal/mol, respectively. Molecular dynamics simulation revealed that these ligands are stable within the M^pro active site. Binding of these ligands is driven by a variety of non-bonded interaction, including polar bonds, H-bonds, van der Waals and salt bridges. The overall conformational dynamics of the complexed-M^pro was slightly altered relative to apo-M^pro. This study demonstrates that three distinct classes molecules, Isavuconazonium (triazole), α-KI (ketoamide) and Pentagastrin (peptide) could serve as potential drugs to treat patients with COVID-19.

Investigation of beta-lactoglobulin derived bioactive peptides against SARS-CoV-2 (COVID-19): in silico analysis

Bilal Çakır, Betül Okuyan, Göksel Şener, Tuğba Tunalı-Akbay, Eur J Pharmacol. 2020 Nov 30;891:173781.

doi: 10.1016/j.ejphar.2020.173781. Online ahead of print.

Abstract

The coronavirus disease of 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which started in late 2019 in Wuhan, China spread to the whole world in a short period of time, and thousands of people have died due to this epidemic. Although scientists have been searching for methods to manage SARS-CoV-2, there is no specific medication against COVID-19 as of yet. Two main approaches should be followed in the treatment of SARS-CoV-2; one of which is to neutralize the virus, and the other is to inhibit the host cell membrane receptors, where SARS-CoV-2 will bind. In this study, peptides derived from beta-lactoglobulin, which inactivates both the virus and its receptors in the host cell, were identified using computer-based in silico analysis. The beta-lactoglobulin derived peptides used in this study were obtained by the treatment of goat milk whey fraction with trypsin. The structure of the peptides was characterized by the liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS), and six beta-lactoglobulin derived peptides were selected as candidate peptides. Subsequently, the effects of peptides on SARS-CoV-2 and host cells were identified using virtual screening. According to the results of this in silico analysis, Ala-Leu-Pro-Met-His-Ile-Arg (ALMPHIR) and Ile-Pro-Ala-Val-Phe-Lys (IPAVFK) peptides were evaluated as potential candidates to be used in the treatment of SARS-CoV-2 after the future in vitro and in vivo studies.

A natural food preservative peptide nisin can interact with the SARS-CoV-2 spike protein receptor human ACE2

Rajarshi Bhattacharya, Aayatti Mallick Gupta, Suranjita Mitra, Sukhendu Mandal, Swadesh R Biswas, Virology. 2021 Jan 2;552:107-111.

doi: 10.1016/j.virol.2020.10.002. Epub 2020 Oct 28.

Abstract

Nisin, a food-grade antimicrobial peptide produced by lactic acid bacteria has been examined for its probable interaction with the human ACE2 (hACE2) receptor, the site where spike protein of SARS-CoV-2 binds. Among the eight nisin variants examined, nisin H, nisin Z, nisin U and nisin A showed a significant binding affinity towards hACE2, higher than that of the RBD (receptor binding domain) of the SARS-CoV-2 spike protein. The molecular interaction of nisin with hACE2 was investigated by homology modeling and docking studies. Further, binding efficiency of the most potent nisin H was evaluated through the interaction of hACE2:nisin H complex with RBD (receptor-binding domain) of SARS-CoV-2 and that of hACE2:RBD complex with nisin H. Here, nisin H acted as a potential competitor of RBD to access the hACE2 receptor. The study unravels for the first time that a globally used food preservative, nisin has the potential to bind to hACE2.

Dalbavancin binds ACE2 to block its interaction with SARS-CoV-2 spike protein and is effective in inhibiting SARS-CoV-2 infection in animal models

Gan Wang, Meng-Li Yang, Zi-Lei Duan, Feng-Liang Liu, Lin Jin, Cheng-Bo Long, Min Zhang, Xiao-Peng Tang, Ling Xu, Ying-Chang Li, Peter Muiruri Kamau, Lian Yang, Hong-Qi Liu, Jing-Wen Xu, Jie-Kai Chen, Yong-Tang Zheng, Xiao-Zhong Peng, Ren Lai, Cell Res. 2020 Dec 1;1-8.

doi: 10.1038/s41422-020-00450-0. Online ahead of print.

Abstract

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic worldwide. Currently, however, no effective drug or vaccine is available to treat or prevent the resulting coronavirus disease 2019 (COVID-19). Here, we report our discovery of a promising anti-COVID-19 drug candidate, the lipoglycopeptide antibiotic dalbavancin, based on virtual screening of the FDA-approved peptide drug library combined with in vitro and in vivo functional antiviral assays. Our results showed that dalbavancin directly binds to human angiotensin-converting enzyme 2 (ACE2) with high affinity, thereby blocking its interaction with the SARS-CoV-2 spike protein. Furthermore, dalbavancin effectively prevents SARS-CoV-2 replication in Vero E6 cells with an EC₅₀ of ~12 nM. In both mouse and rhesus macaque models, viral replication and histopathological injuries caused by SARS-CoV-2 infection are significantly inhibited by dalbavancin administration. Given its high safety and long plasma half-life (8-10 days) shown in previous clinical trials, our data indicate that dalbavancin is a promising anti-COVID-19 drug candidate.

Identification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools

Marek Prachar, Sune Justesen, Daniel Bisgaard Steen-Jensen, Stephan Thorgrimsen, Erik Jurgons, Ole Winther, Frederik Otzen Bagger, Sci Rep. 2020 Nov 24;10(1):20465.

doi: 10.1038/s41598-020-77466-4.

Abstract

The outbreak of SARS-CoV-2 (2019-nCoV) virus has highlighted the need for fast and efficacious vaccine development. Stimulation of a proper immune response that leads to protection is highly dependent on presentation of epitopes to circulating T-cells via the HLA complex. SARS-CoV-2 is a large RNA virus and testing of all of its overlapping peptides in vitro to deconvolute an immune response is not feasible. Therefore HLA-binding prediction tools are often used to narrow down the number of peptides to test. We tested NetMHC suite tools’ predictions by using an in vitro peptide-MHC stability assay. We assessed 777 peptides that were predicted to be good binders across 11 MHC alleles in a complex-stability assay and tested a selection of 19 epitope-HLA-binding prediction tools against the assay. In this investigation of potential SARS-CoV-2 epitopes we found that current prediction tools vary in performance when assessing binding stability, and they are highly dependent on the MHC allele in question. Designing a COVID-19 vaccine where only a few epitope targets are included is therefore a very challenging task. Here, we present 174 SARS-CoV-2 epitopes with high prediction binding scores, validated to bind stably to 11 HLA alleles. Our findings may contribute to the design of an efficacious vaccine against COVID-19.

Toward COVID-19 Therapeutics: A Viewpoint from the Nonprotein Amino Acid Based Synthetic Peptide Design Approach

Sayan Bhattacharjee, ACS Chem Neurosci. 2020 Nov 18;11(22):3701-3703.

doi: 10.1021/acschemneuro.0c00661. Epub 2020 Nov 3.

Abstract

Cell entry, the fundamental step in cross-species transmission of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), is initiated by the recognition of the host cell angiotensin-converting enzyme-2 (ACE2) receptor by the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. To date, several peptides have been proposed against SARS-CoV-2 both as inhibitor agents or as detection tools that can also be attached to the surfaces of nanoparticle carriers. But owing to their natural amino acid sequences, such peptides cannot be considered as efficient therapeutic candidates from a biostability point of view. This discussion demonstrates the design strategy of synthetic nonprotein amino acid substituted peptides with enhanced biostability and binding affinity, the implication of which can make those peptides potential therapeutic agents for inhibition and simple detection tools.

Probiotics-Derived Peptides and Their Immunomodulatory Molecules Can Play a Preventive Role Against Viral Diseases Including COVID-19

Sounik Manna, Trinath Chowdhury, Ranadhir Chakraborty, Santi M Mandal, Probiotics Antimicrob Proteins. 2020 Nov 23;1-13.

doi: 10.1007/s12602-020-09727-7.Online ahead of print.

Abstract

As of recent, the pandemic episode of COVID-19, a severe acute respiratory syndrome brought about by a novel coronavirus (SARS-CoV-2) expanding the pace of mortality, has affected the disease rate profoundly. Invulnerability is the fundamental choice to prevent the ruining event of COVID-19, as the drugs and antibodies are in the phase of preliminary clinical trials. Within this brief period, a few strains of SARS-CoV-2 have been recognized by the vaccine manufacturers, which could be an incorrect guess about the strain that will end up spreading. Since the circulating SARS-CoV-2 strains continue to mutate, immunizations, if at all works, might be for a restricted time. We have not put sufficient time in research to understand the immune responses that correlate with protection as this could help refine vaccines. Here, we have summed up the adequacy of the immunomodulatory component of probiotics for the prevention against viral infections. Furthermore, an in silico data have been provided in support of the “probiotics-derived lipopeptides” role in inactivating spike (S) glycoprotein of SARS-CoV-2 and its host receptor molecule, ACE2. Among well characterized lipopeptides derived from different probiotic strains, subtilisin (Bacillus amyloliquefaciens), curvacin A (Lactobacillus curvatus), sakacin P (Lactobacillus sakei), lactococcin Gb (Lactococcus lactis) was utilized in this study to demonstrate a higher binding proclivity to S-protein of SARS-CoV-2 and human ACE2. The outcome revealed noteworthy capabilities of the lipopeptides, due to their amphiphilic nature, to bind spike protein and receptor molecule, which may act to competitively inhibit the mandatory interaction of SARS-CoV-2 with the host epithelial cell expressing ACE2 for its entry into the cell for reproduction. In the current situation, probiotic treatment alongside chemotherapy may assist in bringing about substantial improvement of the health of COVID-19 patients. At the same time, probiotics may aid towards building up the immune defenses in people to evade COVID-19.

Evolutionary artificial intelligence based peptide discoveries for effective Covid-19 therapeutics

Ritika Kabra, Shailza Singh, Biochim Biophys Acta Mol Basis Dis. 2021 Jan 1;1867(1):165978.

doi: 10.1016/j.bbadis.2020.165978.Epub 2020 Sep 24.

Abstract

An epidemic caused by COVID-19 in China turned into pandemic within a short duration affecting countries worldwide. Researchers and companies around the world are working on all the possible strategies to develop a curative or preventive strategy for the same, which includes vaccine development, drug repurposing, plasma therapy, and drug discovery based on Artificial intelligence. Therapeutic approaches based on Computational biology and Machine-learning algorithms are specially considered, with a view that these could provide a fast and accurate outcome in the present scenario. As an effort towards developing possible therapeutics for COVID-19, we have used machine-learning algorithms for the generation of alignment kernels from diverse viral sequences of Covid-19 reported from India, China, Italy and USA. Using these diverse sequences we have identified the conserved motifs and subsequently a peptide library was designed against them. Of these, 4 peptides have shown strong binding affinity against the main protease of SARS-CoV-2 (M^pro) and also maintained their stability and specificity under physiological conditions as observed through MD Simulations. Our data suggest that these evolutionary peptides against COVID-19 if found effective may provide cross-protection against diverse Covid-19 variants.