In silico comparative study of SARS-CoV-2 proteins and antigenic proteins in BCG, OPV, MMR and other vaccines: evidence of possible putative protective effect

doi:10.21203/rs.3.rs-105598/v1

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In silico comparative study of SARS-CoV-2 proteins and antigenic proteins in BCG, OPV, MMR and other vaccines: evidence of possible putative protective effect

https://doi.org/10.21203/rs.3.rs-105598/v1

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Background: Coronavirus Disease 19 (COVID-19) is a viral pandemic disease that induces severe pneumonia in human. Until now, no effective therapeutic interventions or specific vaccines have been developed. In this paper, we attempt to investigate the putative implication of 12 vaccines, including BCG, OPV and MMR in the protection against COVID-19. First, we compared sequences of the main antigenic proteins in the investigated vaccines and SARS-CoV-2 proteins. Then, we investigated identified segments using a combination of structural and antigenicity prediction tools to predict their immunogenic effect.

Results: A total of 14 highly similar segments were identified in investigated vaccines. After mapping on S and N proteins and analysis of the antigenicity prediction, three segments, in Hepatitis B, Tetanus and Measles proteins showed structural and antigenic properties that can induce possible putative protective effect.

Conclusions: HBV, Tetanus and Measles vaccines should constitute a good candidate for a clinical trial to evaluate their real protective effect against COVID-19.

Bioinformatics

SARS-CoV-2

BCG

OPV

MMR

immunogenicity

Vaccine

Since December 2019, an emerging virus has been spreading worldwide, causing a huge health and economic crisis which is expected to continue for a prolonged period. The new discovered coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the Coronavirus disease (COVID-19), caused a worldwide pandemic state, declared by the World Health Organization (WHO) in March 2020 [1]. So far, SARS-CoV-2 has been responsible for more than half a million fatalities and more than 41 million confirmed cases (from December 8, 2019 to October 21, 2020) [2].

SARS-CoV-2 is an enveloped, positive-sense single-stranded RNA virus. It belongs to the family of Coronaviridae, the subfamily of Orthocoronavirinae and the genus Betacoronavirus [3]. The viral genome of approximately 29903 nucleotides, contains a 5’and 3’ untranslated regions and 11 Open Reading Frames (ORF) encoding 11 proteins of which the Spike (S) and Nucleocapsid (N) proteins identified as the main antigenic proteins [4, 5].

The total number of SARS-CoV-2 affected persons, complicated and death cases varied from one country to another. In the majority of cases, huge health injuries were reported, such as in USA, Brazil, India and Russia causing respectively, 218 131, 153 905, 115 197 and 24 366 deaths and 8 065 615, 5 235 344, 7 597 063, 1 415 316 confirmed cases up to 18 October 2020 [6]. However, in other regions, such as Madagascar, Sierra Leone, Nicaragua and Uruguay seem to be limited. The number of deaths did not exceed 300 up to the same date [6]. These variances can be explained by different factors, such as health infrastructure, mitigation strategy and also cultural behavior [7]. It was also attributed to the vaccination strategies used in those regions. Indeed, it was previously demonstrated that administration of vaccines including attenuated viruses such as OPV (Oral Poliovirus Vaccine), MMR (Measles, Mumps and Rubella vaccines) and BCG (Bacillus Calmette-Guérin) vaccine can improve innate immune response to fight different pathogens. Furthermore, it was recently suggested that adoption of a universal and long-standing BCG policy in those countries could have a protective effect against COVID-19 [7]. Nevertheless, and until now, no comprehensive fundamental evidence showed the relationship between regular vaccination and the acquisition of immunity to SARS-CoV-2. Indeed, a recent epidemiological study, based on a large cohort demonstrated no links between the administration of BCG vaccine and COVID-19 virulence [8] while at the same time, after refining the epidemiological study, a strong correlation was reported [9]. The protective potential of MMR vaccine was also investigated based on bioinformatic analysis of the S protein. However, no similarity with the crystal structure of S protein has been reported [10]. Nevertheless, the use of existing vaccines is of great interest and can help to mitigate the COVID-19 pandemics.

In this paper, we attempt to investigate the putative implication of attenuated vaccines (BCG, OPV and MMR) and 9 other vaccines. We aim to identify amino-acid regions in all SARS-CoV-2 proteins similar to main antigenic proteins in other vaccines which may lead to the production of cross-reactive antibodies against the target agent and SARS-CoV-2 and/or the induction of cellular immunity. To achieve this goal, we used a combination of bioinformatic tools to compare the amino-acid sequences of the main antigenic protein of investigated vaccines and all SARS-CoV-2 proteins as well as to predict immunogenicity of similar identified patterns.

Amino acid sequence alignment and hot spot analysis

The global amino acid identity between the main antigenic protein of investigated vaccines and SARS-CoV-2 proteins does not exceed 63%. For structural proteins, it varied between 21% and 55% (identity levels for the Spike and Matrix proteins respectively with the Polyprotein E1/E2 of Rubella virus and the HAV VP1 protein). For non-structural proteins, identity levels varied between 21 and 63% (identity rates of ORF1a and ORF3a proteins respectively with HBsAg-adr protein of Hepatitis B virus and Tetanus Toxin protein) (Additional material 1).

Similar segments with main vaccine antigenic protein were identified all along structural and non-structural proteins of SARS-CoV-2. The majority were shorter than 5 consecutive amino-acids for all SARS-CoV-2 proteins (Additional material 2-13). Nevertheless, a total of 12 patterns of six to eight similar consecutive amino-acids were identified in comparison against main antigenic proteins in: Poliovirus, Measles, Streptococcus pneumoniae, Tetanus, Mumps, Hepatitis B, Hib and BCG vaccines (Table1). Two similar segments were identified through comparison of Poliovirus, Measles, PCV10 and Hib proteins and SARS-CoV-2 structural proteins (S and N) and also non-structural proteins (ORF 1a, ORF 6 and ORF 8). While, tetanus, Mumps, Hepatitis B and BCG antigenic proteins showed no more than one similar segment with SARS-CoV-2 proteins (Table1). Among described peptides, seven were similar to others in S protein, obtained with antigenic proteins in poliovirus Sabin 3, S pneumoniae, tetanus, Mumps, Hepatitis B and Hib vaccines. The patterns length varied between six and seven amino acids. Also, one peptide of eight amino acids (GTSPARMA) detected in the Poliovirus VP1 sequence matched with the N protein of the SARS-CoV-2.

We also identified two discontinuous patterns of 10 amino-acids (DISGFNSSVI, MSLSLLDLYL) in the tetanus toxin and the hemagglutinin measles proteins which present 90% and 80% similarity with another segments (DISGINASVV, IELSLIDFYL) in the S and ORF7b proteins of SARS-CoV-2 respectively.

Table1: Description of similar patterns of more than 5 amino-acids obtained in vaccine antigenic proteins and SARS-CoV-2 proteins

Vaccine	N° of similar segment	Vaccine protein			SARS-CoV-2 Protein
Vaccine	N° of similar segment	Designation	Segment	Position	Designation	Segment	Position
Poliovirus	2	VP1 protein (Sabin 1)	GTAPARIS	188-195	N	GTSPARMA	203-211
Poliovirus	2	VP1 protein (Sabin 3)	LDPLSE	289-295	S	LDPLSE	293-299
Measles	2	Fusion protein	QECLRG	359-364	ORF6	QECVRG	21-27
Measles	2	Fusion protein	IQVGSRR	433-440	ORF8	IRVGARK	47-54
*Streptoccocus pneumonea*	2	Capsular polysaccharide biosynthesis protein (serotype19F, 18C, 14, 7, 4, 1)	IGFLAGVI	182-190	S	LGFIAGLI	1218-1226
*Streptoccocus pneumonea*	2	Capsular polysaccharide biosynthesis protein (serotype19F, 18C, 14, 5)	SSVAFA	33-39	S	NSVAYS	703-708
*Hib*	2	Capsular polysaccharide biosynthesis protein	KNINDS	210-215	S	KNLNES	1191-1196
*Hib*	2	Capsular polysaccharide biosynthesis protein	FILNKKI	73-79	ORF1a	FLLNKEM	3183-3189
BCG	1	Immunogenic protein MPB64	IFMLVT	5-11	E	VFLLVT	25-31
Tetanus	1	Toxin protein	NILMQY	84-90	S	NLLLQY	751-756
Mumps	1	Fusion protein	DISTEL	448-454	S	DISTEI	467-473
Hepatitis B	1	HBs Ag-adr	PGTSTTS	111-117	S	PGTNTSN	600-606

Immunogenicity prediction

Our analysis has been conducted in two inspections. First, we focused on characterizing the immunogenicity of the matching sequences with S and N proteins for their involvement in modulating the immune response of the host [11, 12].

Regarding the pattern identified in N protein, no significant similarity was obtained with the crystal structure of the corresponding protein. Among the seven patterns identified in S protein, four segments (LDPLSE, NSVAYS, NLLLQY, PGTNTSN) respectively from Polio, PCV10, Tetanus and HBV vaccines have been mapped to the structure of the spike protein (figure 1A). The three other patterns (LGFIAGLI, KNLNE and DISTEI) are not solved by the electron density map from the Cryo-EM structure. Among the four retained patterns, except for the segments PGTNTSN and LGFIAGLI, none of the other peptides show a putative interaction with one of the MHC receptors predicted by IEDB analysis resource NetMHCpan. However, the prediction for both of these peptides shows a weak peptide score of 0.07 and 0.02 respectively (0 indicates no MHC capacity, and 1 indicates a high probability). the segment PGTNTSN, present in the Hbs Ag of Hepatitis B virus adr strain, is situated in a turn region and shows the highest level of exposure to the solvent (figure 1 B) with an average SASA value of 407 Å². Thus, among the seven candidate segments, only PGTNTSN shows a putative humoral immunogenicity predicted by EpiJen ranked as the fourth best match with a predicted IC50 Value of 4.33. (Figure 1 C)

In the second inspection, we focused on a list of hits that belong to any of the investigated vaccine sequences and that match any of the other proteins of SARS-CoV-2. All the patterns have been explored for their antigenic potential using EpiJen and IEDB NetMHCpan methods. They don’t show any putative antigenicity properties predicted by the servers.

Discontinuous patterns with more than 10 residues are discarded from the analysis as they show low levels of similarity. Nevertheless, we have retained two segments in Tetanus toxin protein (DISGFNSSV) and chain A, hemagglutinin Protein of the measles virus (MSLSLLDLYL) that significantly matched with SARS-CoV-2 Spike and ORF7b proteins. The segment DISGINASVV of the S protein that matches the sequence DISGFNSSVI of the tetanus toxin shows a putative interaction with one of the MHC receptors predicted by IEDB analysis resource NetMHCpan. These two matching sequences showed high peptide scores of 0.88 and 0.76 (0 indicates no MHC capacity, and 1 indicates a high probability) respectively for SARS-CoV-2 S protein of and the tetanus toxine protein. Regarding segments ORF7b and Measles hemagglutinin Protein, both overlap significantly with regions of putative T-cell antigenicity. This identified segment corresponds to a random coil segment (MSLS) spanned by an alpha helix of six residues (LLDLYL) in the crystal structure of the hemagglutinin [13]. The segment also interacts with a large pocket formed mainly by four strands of a beta-sheet containing many aromatic amino acids. The pocket resembles the grooves of the MHC I and MHC II molecules (Figure 2).

In this study, we investigated the potential of protective effects against COVID-19 induced by existing vaccines. The use of existing vaccines can help to mitigate the COVID-19 pandemics very quickly with a safe and validated vaccine while waiting for the development of specific vaccines or preventive therapies. To achieve this goal, we used a combination of amino acid alignment, structural and antigenicity prediction tools to evaluate main antigenic proteins in 12 worldwide used vaccines including BCG, OPV and MMR vaccines.

In our study, hotspot analysis demonstrated that main detected patterns are shorter than 5 amino acids and therefore cannot constitute a putative T-cell epitope. Nevertheless, 12 motifs of 6 to 8 amino-acids were investigated. After mapping on S protein and analysis of the antigenicity prediction, only the pattern ‘PGTNTSN’ detected in HBsAg of Hepatitis B virus corresponds to an exposed site in S protein and showed the highest values of accessible surface area. Thus, its structural properties are in agreement with its putative neutralizing capacity. Naturally, the antibodies would be able to recognize the targeted epitope in the integral assembled structure of the virus and therefore, the epitope must be accessible at the surface of the spike protein. On the other hand, in their recent attempt to establish the antigenicity map of SARS-CoV-2, Zhang et al (2020) [12] have found that a segment called IDh spanning residues 522–646 was found to induce a positive reaction by B-cells from convalescent sera from COVID-19 patients. The pattern ‘PGTNTSN’ is included in the IDh epitope and we were able to identify strong prediction metrics using the EpiJen server. Therefore, the induced immunological reaction by this segment would be humoral response. Furthermore, our results are in agreement with the work achieved by Tajiri et al (2010) [14]. The authors showed that two regions of HBsAg (residues 104-123 and 108-123) containing the epitope matching the ‘PGTNTSN’ segment of SARS-CoV-2 are capable of binding two human monoclonal antibodies which highlights the immunogenic capability of these segments. Nevertheless, only, randomized controlled trials can provide evidence of induced protective effect against COVID-19. In many countries, the HBV vaccine is known to be recommended or mandatory for healthcare and wet lab workers. It is therefore worth it investigating the relationship between the prevalence of SARS-CoV-2 and HBV vaccination.

Interestingly, our analysis showed the presence of two segments of 10 aa from the Tetanus toxin protein and chain A of the Measles hemagglutinin Protein, similar to another in the S and ORF7b proteins. The segment ‘DISGINASV’, matching with the toxin tetanus protein has been described previously to be part of an antigenic peptide in the S protein of SARS-CoV [15]. Regarding the segment matching with the ORF7b protein. Although this protein is suggested to have an accessory function whose role is yet to be determined [16], we cannot exclude its possible immunogenic role. On the other hand, we have also recorded significant global identity level between Measles fusion and hemagglutinin proteins and SARS-CoV-2 spike, envelope and matrix proteins (45-50%) (suppl mat. 1). Furthermore, other study using other Measles and Rubella sequences than those of vaccinal Measles and Rubella strains (Edmonston Measles and Rubella Wistar RA 27/3 strains) revealed similarity between the N terminal region of SARS-COV-2 Spike protein and the Fusion protein of Measles virus as well as with the envelope protein of the Rubella virus. Nevertheless, no similarity was obtained with the crystal structure [10]. The Measles vaccine is an attenuated vaccine administered as part of MR (Measles and Rubella) or MMR (Measles, Mumps and Rubella). It was previously demonstrated that attenuated vaccines such as OPV, BCG and MMR can improve the innate immune response to subsequent pathogens [17]. These non-specific effects of live vaccines involve the trained immunity which refers to the memory-like characteristics of innate immune cells [18]. Indeed, following exposure to a primary stimulus like a vaccine or a microbial component, innate immune cells, especially monocytes and NK-cells, undergo epigenetic reprogramming that subsequently regulate cytokine production and cell metabolism and collectively enhance responsiveness to an unrelated secondary stimulus. In this line, observational studies reported a decrease in hospitalization rate and overall mortality among immunized children with live attenuated vaccines [19]. Furthermore, currently, pediatric populations seem to be protected against COVID-19, especially in low and middle incomes countries. The long-standing use of attenuated vaccine, with high coverage, could explain the low symptomatic infection rate among children. Thus, MMR vaccine could also constitute a good candidate for a clinical trial to evaluate its real protective effect against COVID-19.

The control of COVID-19 will be possible only after a large immunization of the world population through infection of the majority of the world population or the use of an effective vaccine. Nevertheless, conception, validation and mass production of an effective and safe vaccine is difficult to achieve. Thus, the use of existing vaccines can help to mitigate the COVID-19 pandemics very quickly. This study demonstrates a possible putative protective effect of HBV, Tetanus and Measles vaccines which has, certainly, to be confirmed by randomized controlled trials. Thus, HBV, Tetanus and Measles vaccines should constitute a good candidate for a clinical trial to evaluate their real protective effect against COVID-19.

Investigated Vaccines and Sequences

Our study focused on 12 vaccines including attenuated vaccines (BCG, OPV, MMR vaccines) and inactivated ones (Tetanus, Corynebacterium diphtheriae, Bordetella pertissus, Hepatitis B, Hepatitis A, Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae vaccines (PCV10) (Table 2).

The full amino-acid sequences of main antigenic proteins (n=30) corresponding to the 12 investigated vaccines were obtained from NCBI Genbank database. Accession numbers are presented in Table 1. In addition, the amino-acid sequences of the structural proteins (Spike (S), Envelope (E), Matrice (M), N (Nucleocapsid) and non-structural proteins (ORF1ab, ORF1a, ORF3a, ORF6, ORF7a, ORF7ab, ORF8 and ORF10) of SARS-CoV-2 Wuhan reference strain (NC_045512) were obtained.

Table 2: vaccines and corresponding antigenic proteins investigated in this study

Vaccine	Protein	Accession N°	Reference
Tetanus	Toxin protein	AAA23282.1	24
Corynebacterium diphtheriae	Toxin protein	CAA00374.1	24
Hepatitis B	HBsAg-adw2	AAW65557.1	25
Hepatitis B	HBsAg-adr	AAW65588.1
Bordetella pertussis	Toxin protein	AQW64178.1	24
Measles	Hemagglutinin protein	AAF85705.1
Measles	Fusion protein	AAF85704.1	26
Rubella	Polyprotein E1/E2	ACN50046.1	26
Mumps	Fusion protein	ACN50030.1
Mumps	Hemagglutinin/neuraminidase protein	ACN50032.1	26
Hepatitis A	VP1 protein	AAA45466.1
Hepatitis A	VP3 protein	AAA45466.1	27, 28
Bacillus Calmette-Guérin (BCG)	Immunogenic protein MPB83	BAA11027.1
	Immunogenic protein MPB70	BAA07402.1	29-31
	Immunogenic protein MPB64	AIC33023.1
Hemophilus influenzae serotype B (Hib)	Capsulation protein	CWW30252.1	24
Hemophilus influenzae serotype B (Hib)	Capsular polysaccharide biosynthesis protein	WP_015702013.1
Poliovirus	VP1 protein (Sabin 1 strain)	AAL89597.1	32
	VP1 protein (Sabin 2 strain)	AAL92486.1
	VP1 protein (Sabin 3 strain)	AAL89592.1
Streptococcus pneumoniae (PCV10)	Capsular polysaccharide biosynthesis protein [serotype 19F]	AEO88919.1	33
	Capsular polysaccharide biosynthesis protein [serotype 23F]	AAC69522.1
	Capsular polysaccharide biosynthesis protein [serotype 18C]	CAI33577.1
	Capsular polysaccharide biosynthesis protein [serotype 14]	CAI33319.1
	Capsular polysaccharide biosynthesis protein [serotype 9V]	CAI33023.1
	Capsular polysaccharide biosynthesis protein [serotype 7F]	CAI32924.1
	Capsular polysaccharide biosynthesis protein [serotype 6B]	AAK20683.1
	Capsular polysaccharide biosynthesis protein [serotype 5]	CAI32793.1
	Capsular polysaccharide biosynthesis protein [serotype 1]	COS99248.1
	Capsular polysaccharide biosynthesis protein [serotype 4]	AAK20668.1

Amino acid sequence alignment and hot spot analysis

Identification of similar segment, including identical amino-acids and/or similar amino-acids (with similar biochemical properties), was assessed using Blastp homology search by querying the protein sequences of SARS-CoV-2 over the set of antigenic sequences of the vaccines [20]. Pairwise alignments obtained from Blastp were explored and analysed using BioEdit software, version 7.2.5 (http://www.mybiosoftware.com/bioedit-7-0-9-biological-sequence-alignment-editor.html).

Structural analysis and antigenicity prediction

The structure of the SARS-CoV-2 spike protein was obtained from the PDB entry 7BYR corresponding to 99.5% of sequence identity with QJT73034.1 entry [21]. The segments matching one of the sequences of S and N proteins were mapped on the structure. The Solvent Accessible Surface Area per residue was calculated using freesasa [21]. The T-cell epitope prediction was conducted using EpiJen [22], and the IEDB analysis resource NetMHCpan [23] methods by uploading the primary structure of SARS-CoV-2 protein. For the latter method, we have considered all the possible human HLA alleles for MHC class I. In order of a pattern to be retained, it has to show a good quality local alignment with no indels and no more than two successive dissimilar residues. The matching pattern of the query has to show significant antigenicity prediction at least for one of the methods, EpiJen or IEDB NetMHCpan. For the latter we have fixed a cutoff of peptide score no less than 0.1. For EpiJen the rank of the evaluated peptide has to be at the best top 10 predictions returned by the server.

Ethics approval and consent to participate: Not applicable

Consent for publication: Not applicable

Availability of data and materials: All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Competing interests: The authors declare that they have no competing interests.

Funding: This study was funded by the Tunisian ministry of higher education and Scientific Research (Research laboratory: Virus, Vectors and Hosts). It was also partially supported by the European project PHINDaccess: Strengthening Omics data analysis capacities in pathogen-host interaction (Grant agreement ID: 811034).

Authors' contributions:

SH-B and KG designed the study, SH-B and HO wrote the papers, HO, RT, KA and M L contributed to carry out analysis, SH-B, IBM, MK and HT validated the study. All authors read and approved the final manuscript.

Acknowledgement: This study was funded by the Tunisian ministry of higher education and Scientific Research (Research laboratory: Virus, Vectors and Hosts). It was also partially supported by the European project PHINDaccess: Strengthening Omics data analysis capacities in pathogen-host interaction (Grant agreement ID: 811034).

Authors’ Information

S Haddad-Boubaker, PhD, HDR in Virology from the Faculty of Sciences of Tunis. She is an Assistant Professor in the Laboratory of Clinical Virology, at Pasteur Institute of Tunis, which acts as the WHO Regional Reference Laboratory for Poliomyelitis and Measles in the EMRO region. She is also a Professor of Medical Virology and the coordinator of the Microbiology section in the High Institute of health techniques in Tunis, Tunisia. Her research interest includes molecular characterization and omics data analysis of Human viruses, especially poliovirus, enteric viruses and SARS-CoV2.

H Othman, PhD is a bioinformaticist at the Sydney Brenner Institute for Molecular Bioscience at the University of the Witwatersrand. His main interests are pharmacogenomics, Molecular modeling, and data science. He is an avid supporter of reproducible research practices and data sharing trying to increase awareness about these issues in bioinformatics and genomics fields.

R Touati, PhD in electrical engineering from the National Engineering School of Tunisia (ENIT). Currently, she has a Post-Doctoral position at the Laboratory of Human Genetics (LR99ES10) at the Faculty of Medicine of Tunis (FMT). Her research interest includes genomic signal processing, bioinformatics, pattern recognition and machine learning.

K Ayouni, PhD student in the Laboratory of Clinical Virology, at Pasteur Institute of Tunis, Tunisia.

M Lakhal, PhD student in Human Genetics at the Faculty of Medicine of Tunis, Tunisia.

Prof I Ben Mustapha, MD. She is a Professor in Immunology in the Faculty of Medicine of Tunis and a head of research Team in the Laboratory of Transmission, Control and Immunobiology of Infections in Institut Pasteur de Tunis, Tunisia.

K Ghedira, PhD in Bioinformatics. He is an assistant professor in bioinformatics at the Institut Pasteur de Tunis. He is a head of research team in the Laboratory of Biomathematics, Biomathematics and Biostatistics in Institut Pasteur de Tunis, Tunisia. His research interests are mainly focused on OMICS data integration and functional genomics.

Prof. M Kharrat, PhD in Human Genetics from the Faculty of Medicine of Tunis (FMT). He is Professor in Human Genetics in 2006 at the Faculty of Medicine of Tunis (FMT). He is the head of the Genetic Human laboratory (LR99ES10) at the Faculty of Medicine of Tunis (FMT). His research interests include Human Genetics.

Prof. H Triki, MD: She is Professor in Virology in 2006 at the Faculty of Medicine of Tunis (FMT). She is the head of laboratory of Clinical Virology, which acts as the WHO Regional Reference Laboratory for Poliomyelitis and Measles in the EMRO region. In 2018, she was assigned as Director of the Clinical Investigation Center entitled: “Transmissible diseases: Natural history and innovated tools for diagnostic, prevention and treatment” in Pasteur Institute of Tunis.

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additionaltable1.docx
Additional table 1: Global amino-acid identities between structural protein sequences of Sars-CoV-2 and main antigenic proteins of investigated vaccines.
additionaltable1.docx
Additional table 1: Global amino-acid identities between structural protein sequences of Sars-CoV-2 and main antigenic proteins of investigated vaccines.
Additionalmat2130711.docx
Additional material 2 -13 :Similar patterns identified between SARS-CoV-2 proteins and antigenic proteins in investigated vaccines
Additionalmat2130711.docx
Additional material 2 -13 :Similar patterns identified between SARS-CoV-2 proteins and antigenic proteins in investigated vaccines

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In silico comparative study of SARS-CoV-2 proteins and antigenic proteins in BCG, OPV, MMR and other vaccines: evidence of possible putative protective effect

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