Biotechnology & Biotechnological Equipment
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/tbeq20
The virus that shook the world: questions and
answers about SARS-CoV-2 and COVID-19
Radostina Alexandrova , Pencho Beykov , Dobrin Vassilev , Marko Jukić &
Črtomir Podlipnik
To cite this article: Radostina Alexandrova , Pencho Beykov , Dobrin Vassilev , Marko Jukić
& Črtomir Podlipnik (2021) The virus that shook the world: questions and answers about
SARS-CoV-2 and COVID-19, Biotechnology & Biotechnological Equipment, 35:1, 74-102, DOI:
10.1080/13102818.2020.1847683
To link to this article: https://doi.org/10.1080/13102818.2020.1847683
© 2020 The Author(s). Published by Informa
UK Limited, trading as Taylor & Francis
Group.
Published online: 08 Dec 2020.
Submit your article to this journal
Article views: 1490
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View Crossmark data
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=tbeq20
,BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT
2020, VOL. 35, NO. 1, 74–102
https://doi.org/10.1080/13102818.2020.1847683
The virus that shook the world: questions and answers about SARS-CoV-2
and COVID-19
Radostina Alexandrovaa, Pencho Beykova,b, Dobrin Vassilevc, Marko Jukicd,e and Crtomir Podlipnikf
a
Department of Pathology Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of
Sciences, Sofia, Bulgaria; bFaculty of Chemistry and Pharmacy, Sofia University “St. Kliment Ohridski”, Sofa, Bulgaria; c“Alexandrovska”
University Hospital, Medical University of Sofia, Sofia, Bulgaria; dLaboratory of Physical Chemistry and Chemical Thermodynamics,
Faculty of Chemistry and Chemical Technology, University of Maribor, Maribor, Slovenia; eNatural Sciences and Information
Technologies, Faculty of Mathematics, University of Primorska, Koper, Slovenia; fDepartment of Physical Chemistry, Faculty of
Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia
ABSTRACT ARTICLE HISTORY
SARS-CoV-2 is an emerging human beta-coronavirus that caused the COVID-19 (Coronavirus Received 1 October 2020
Disease 19) pandemic, the most significant health and social crisis in the last 100 years. SARS- Accepted 3 November 2020
CoV-2 is not only a respiratory virus; the symptoms of COVID-19 can include gastrointestinal,
KEYWORDS
neurological, renal, cardiovascular and other complications. A large part of SARS-CoV-2 infected
Coronaviruses; SARS-CoV-2;
individuals are asymptomatic or have mild symptoms, around 20% of COVID-19 cases require COVID-19; model systems;
hospitalization, and 5% can become critically ill. This review summarizes data on the biology of therapeutical
the virus and its pathological manifestations, antiviral immune response, information on the agents; vaccines
experimental models used in the related studies, treatment approaches and vaccine strategies.
Coronaviruses fusion and virus entry (the S2 domain plays the leading
role in this process) after processing by cellular transmem-
General information
brane serine protease 2 (TMPRSS2) [2]. The S glycoprotein
Coronaviruses (CoVs) belong to the subfamily is also the main target for neutralizing antibodies [3] (see
Coronavirinae in the family Coronaviridae, order Figure 2A). The interaction of Spike’s RBD domain with
Nidovirales (according to the International Committee the host receptor ACE2 is shown in Figure 2B.
on Taxonomy of Viruses). CoVs are enveloped viruses,
65–125 nm in diameter, which possess a relatively
Viral proteins
large single-stranded, positive-sense RNA genome of
around 27–32 kb - the largest known genomes for The understanding of the SARS-CoV viral proteins allows
RNA viruses. Currently, the most famous virus from a rational approach to the development of more effect-
the coronaviridae family, SARS-CoV-2 has a genome ive antiviral drugs [5–7]. The proteins of SARS-CoV (pre-
length of 29.881 kb (GenBank No. MN908947) and enc- sented in Table 1) consist of two major polyproteins:
odes 9860 amino acids [1]. The name “Corona” repre- ORF1a and ORF1ab (which cleave proteolytically to form
sents the crown-like spikes on the outer surface of the 16 non-structural proteins); four structural proteins: spike
virus (the word ‘corona’ means crown in Latin). (S), envelope (E), membrane (M) and nucleocapsid (N);
The morphology of coronavirus (left) and the and eight accessory proteins: ORF3a, ORF3b (NP
organisation of the viral genomes of SARS-CoV, MERS- _828853.1, not present in SARS-CoV-2), ORF6, ORF7a,
CoV and SARS-CoV-2 are illustrated in Figure 1. ORF7b, ORF8a, ORF8b and ORF9b (NP _828859.1, not
The spike (S) glycoprotein is responsible for the bind- present in SARS CoV-2) [5]. None of the accessory SARS-
ing of the coronavirus to the host cell (this function is CoV proteins is essential for viral replication, but some of
performed by the S1 part that contains the receptor-bind- them play a role in viral pathogenesis, for example,
ing domain of the virus - RBD) and mediates membrane some of them modulate interferon signalling pathways
CONTACT Radostina Alexandrova Department of Pathology Institute of Experimental Morphology, Pathology and
Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria.
ß 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
, BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT 75
Figure 1. Coronavirus morphology along with the organization of the genome of SARS-CoV, MERS-CoV and SARS-CoV-2.
Figure 2. The structure of SARS-CoV-2 Spike protein with neutralizing antibody (A) and the structure of the complex between
Receptor ACE2 and RBD domain (B). Images were generated using Yasara View [4].
and the production of pro-inflammatory cytokines [8]. genera: Alphacoronavirus (a), Betacoronavirus (b),
Like SARS-CoV, SARS-CoV-2 lacks the haemagglutinin Gammacoronavirus (c) and Deltacoronavirus (d)
esterase gene found in human coronavirus (hCoV) HKU1 [19–22]. The alpha-CoVs and beta-CoVs infect only
[8]. The spike protein [2], envelope protein [9,10], mem- mammals inducing mainly respiratory, gastrointes-
brane protein, nucleocapsid protein [11], 3CL protease tinal and neurological diseases. The gamma-CoVs and
[12], papain-like protease [13], RNA polymerase [14] and delta-CoVs affect birds, but some of them can also
helicase [15] have been proposed as viable targets for be pathogenic for mammals.
antiviral drugs [16–18]. Examples of some viral proteins Currently, there are seven coronaviruses known to
listed above are presented in Figure 3. be pathogenic for humans (SARS-CoV, MERS-CoV, 229E,
NL63, OC43, HKU1, as well as the new SARS-CoV-2) and
all of them have a zoonotic origin from bats, mice or
Family members
domestic animals. Four of them, HCoV-229E and HCoV-
Based on their phylogenetic relationships and NL63 (a-CoVs) as well as HCoV-OC43 and HCoV-HKU1
genomic structures, CoVs are divided into four (b-CoVs), induce mild upper respiratory diseases
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/tbeq20
The virus that shook the world: questions and
answers about SARS-CoV-2 and COVID-19
Radostina Alexandrova , Pencho Beykov , Dobrin Vassilev , Marko Jukić &
Črtomir Podlipnik
To cite this article: Radostina Alexandrova , Pencho Beykov , Dobrin Vassilev , Marko Jukić
& Črtomir Podlipnik (2021) The virus that shook the world: questions and answers about
SARS-CoV-2 and COVID-19, Biotechnology & Biotechnological Equipment, 35:1, 74-102, DOI:
10.1080/13102818.2020.1847683
To link to this article: https://doi.org/10.1080/13102818.2020.1847683
© 2020 The Author(s). Published by Informa
UK Limited, trading as Taylor & Francis
Group.
Published online: 08 Dec 2020.
Submit your article to this journal
Article views: 1490
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=tbeq20
,BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT
2020, VOL. 35, NO. 1, 74–102
https://doi.org/10.1080/13102818.2020.1847683
The virus that shook the world: questions and answers about SARS-CoV-2
and COVID-19
Radostina Alexandrovaa, Pencho Beykova,b, Dobrin Vassilevc, Marko Jukicd,e and Crtomir Podlipnikf
a
Department of Pathology Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of
Sciences, Sofia, Bulgaria; bFaculty of Chemistry and Pharmacy, Sofia University “St. Kliment Ohridski”, Sofa, Bulgaria; c“Alexandrovska”
University Hospital, Medical University of Sofia, Sofia, Bulgaria; dLaboratory of Physical Chemistry and Chemical Thermodynamics,
Faculty of Chemistry and Chemical Technology, University of Maribor, Maribor, Slovenia; eNatural Sciences and Information
Technologies, Faculty of Mathematics, University of Primorska, Koper, Slovenia; fDepartment of Physical Chemistry, Faculty of
Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia
ABSTRACT ARTICLE HISTORY
SARS-CoV-2 is an emerging human beta-coronavirus that caused the COVID-19 (Coronavirus Received 1 October 2020
Disease 19) pandemic, the most significant health and social crisis in the last 100 years. SARS- Accepted 3 November 2020
CoV-2 is not only a respiratory virus; the symptoms of COVID-19 can include gastrointestinal,
KEYWORDS
neurological, renal, cardiovascular and other complications. A large part of SARS-CoV-2 infected
Coronaviruses; SARS-CoV-2;
individuals are asymptomatic or have mild symptoms, around 20% of COVID-19 cases require COVID-19; model systems;
hospitalization, and 5% can become critically ill. This review summarizes data on the biology of therapeutical
the virus and its pathological manifestations, antiviral immune response, information on the agents; vaccines
experimental models used in the related studies, treatment approaches and vaccine strategies.
Coronaviruses fusion and virus entry (the S2 domain plays the leading
role in this process) after processing by cellular transmem-
General information
brane serine protease 2 (TMPRSS2) [2]. The S glycoprotein
Coronaviruses (CoVs) belong to the subfamily is also the main target for neutralizing antibodies [3] (see
Coronavirinae in the family Coronaviridae, order Figure 2A). The interaction of Spike’s RBD domain with
Nidovirales (according to the International Committee the host receptor ACE2 is shown in Figure 2B.
on Taxonomy of Viruses). CoVs are enveloped viruses,
65–125 nm in diameter, which possess a relatively
Viral proteins
large single-stranded, positive-sense RNA genome of
around 27–32 kb - the largest known genomes for The understanding of the SARS-CoV viral proteins allows
RNA viruses. Currently, the most famous virus from a rational approach to the development of more effect-
the coronaviridae family, SARS-CoV-2 has a genome ive antiviral drugs [5–7]. The proteins of SARS-CoV (pre-
length of 29.881 kb (GenBank No. MN908947) and enc- sented in Table 1) consist of two major polyproteins:
odes 9860 amino acids [1]. The name “Corona” repre- ORF1a and ORF1ab (which cleave proteolytically to form
sents the crown-like spikes on the outer surface of the 16 non-structural proteins); four structural proteins: spike
virus (the word ‘corona’ means crown in Latin). (S), envelope (E), membrane (M) and nucleocapsid (N);
The morphology of coronavirus (left) and the and eight accessory proteins: ORF3a, ORF3b (NP
organisation of the viral genomes of SARS-CoV, MERS- _828853.1, not present in SARS-CoV-2), ORF6, ORF7a,
CoV and SARS-CoV-2 are illustrated in Figure 1. ORF7b, ORF8a, ORF8b and ORF9b (NP _828859.1, not
The spike (S) glycoprotein is responsible for the bind- present in SARS CoV-2) [5]. None of the accessory SARS-
ing of the coronavirus to the host cell (this function is CoV proteins is essential for viral replication, but some of
performed by the S1 part that contains the receptor-bind- them play a role in viral pathogenesis, for example,
ing domain of the virus - RBD) and mediates membrane some of them modulate interferon signalling pathways
CONTACT Radostina Alexandrova Department of Pathology Institute of Experimental Morphology, Pathology and
Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria.
ß 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
, BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT 75
Figure 1. Coronavirus morphology along with the organization of the genome of SARS-CoV, MERS-CoV and SARS-CoV-2.
Figure 2. The structure of SARS-CoV-2 Spike protein with neutralizing antibody (A) and the structure of the complex between
Receptor ACE2 and RBD domain (B). Images were generated using Yasara View [4].
and the production of pro-inflammatory cytokines [8]. genera: Alphacoronavirus (a), Betacoronavirus (b),
Like SARS-CoV, SARS-CoV-2 lacks the haemagglutinin Gammacoronavirus (c) and Deltacoronavirus (d)
esterase gene found in human coronavirus (hCoV) HKU1 [19–22]. The alpha-CoVs and beta-CoVs infect only
[8]. The spike protein [2], envelope protein [9,10], mem- mammals inducing mainly respiratory, gastrointes-
brane protein, nucleocapsid protein [11], 3CL protease tinal and neurological diseases. The gamma-CoVs and
[12], papain-like protease [13], RNA polymerase [14] and delta-CoVs affect birds, but some of them can also
helicase [15] have been proposed as viable targets for be pathogenic for mammals.
antiviral drugs [16–18]. Examples of some viral proteins Currently, there are seven coronaviruses known to
listed above are presented in Figure 3. be pathogenic for humans (SARS-CoV, MERS-CoV, 229E,
NL63, OC43, HKU1, as well as the new SARS-CoV-2) and
all of them have a zoonotic origin from bats, mice or
Family members
domestic animals. Four of them, HCoV-229E and HCoV-
Based on their phylogenetic relationships and NL63 (a-CoVs) as well as HCoV-OC43 and HCoV-HKU1
genomic structures, CoVs are divided into four (b-CoVs), induce mild upper respiratory diseases
