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Article ; Online: Reduced Binding between Omicron B.1.1.529 and the Human ACE2 Receptor in a Surrogate Virus Neutralization Test for SARS-CoV-2.

Hoffman, Tove / Kolstad, Linda / Akaberi, Dario / Järhult, Josef D / Rönnberg, Bengt / Lundkvist, Åke

2023 Volume 15, Issue 6

Abstract: The current gold standard assay for detecting neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the conventional virus neutralization test (cVNT), which requires infectious virus and a biosafety level ... ...

Abstract	The current gold standard assay for detecting neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the conventional virus neutralization test (cVNT), which requires infectious virus and a biosafety level 3 laboratory. Here, we report the development of a SARS-CoV-2 surrogate virus neutralization test (sVNT) that, with Luminex technology, detects NAbs. The assay was designed to mimic the virus-host interaction and is based on antibody blockage between the human angiotensin-converting enzyme 2 (hACE2) receptor and the spike (S) protein of the Wuhan, Delta, and Omicron (B.1.1.529) variants of SARS-CoV-2. The sVNT proved to have a 100% correlation with a SARS-CoV-2 cVNT regarding qualitative results. Binding between the hACE2 receptor and the S1 domain of the B.1.1.529 lineage of the Omicron variant was not observed in the assay but between the receptor and an S1 + S2 trimer and the receptor binding domain (RBD) in a reduced manner, suggesting less efficient receptor binding for the B.1.1.529 Omicron variant. The results indicate that the SARS-CoV-2 sVNT is a suitable tool for both the research community and the public health service, as it may serve as an efficient diagnostic alternative to the cVNT.
MeSH term(s)	Humans ; Neutralization Tests ; Angiotensin-Converting Enzyme 2 ; SARS-CoV-2/genetics ; COVID-19/diagnosis ; Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Viral
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus ; Antibodies, Viral ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-05-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15061280
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Article ; Online: SARS-CoV-2 in hospital indoor environments is predominantly non-infectious.

Krambrich, Janina / Akaberi, Dario / Ling, Jiaxin / Hoffman, Tove / Svensson, Lennart / Hagbom, Marie / Lundkvist, Åke

Virology journal

2021 Volume 18, Issue 1, Page(s) 109

Abstract: Background: The ongoing SARS-CoV-2 pandemic has spread rapidly worldwide and disease prevention is more important than ever. In the absence of a vaccine, knowledge of the transmission routes and risk areas of infection remain the most important existing ...

Abstract	Background: The ongoing SARS-CoV-2 pandemic has spread rapidly worldwide and disease prevention is more important than ever. In the absence of a vaccine, knowledge of the transmission routes and risk areas of infection remain the most important existing tools to prevent further spread. Methods: Here we investigated the presence of the SARS-CoV-2 virus in the hospital environment at the Uppsala University Hospital Infectious Disease ward by RT-qPCR and determined the infectivity of the detected virus in vitro on Vero E6 cells. Results: SARS-CoV-2 RNA was detected in several areas, although attempts to infect Vero E6 cells with positive samples were unsuccessful. However, RNase A treatment of positive samples prior to RNA extraction did not degrade viral RNA, indicating the presence of SARS-CoV-2 nucleocapsids or complete virus particles protecting the RNA as opposed to free viral RNA. Conclusion: Our results show that even in places where a moderate concentration (Ct values between 30 and 38) of SARS-CoV-2 RNA was found; no infectious virus could be detected. This suggests that the SARS-CoV-2 virus in the hospital environment subsides in two states; as infectious and as non-infectious. Future work should investigate the reasons for the non-infectivity of SARS-CoV-2 virions.
MeSH term(s)	Animals ; COVID-19/transmission ; Cell Line ; Chlorocebus aethiops ; Confined Spaces ; Cross Infection/epidemiology ; Cross Infection/virology ; Disease Transmission, Infectious/statistics & numerical data ; Environmental Monitoring/methods ; Hospitals ; Humans ; Risk ; SARS-CoV-2/growth & development ; Ventilation/methods ; Vero Cells
Language	English
Publishing date	2021-06-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1743-422X
ISSN (online)	1743-422X
DOI	10.1186/s12985-021-01556-6
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Article ; Online: Comparative genome analysis of Alkhumra hemorrhagic fever virus with Kyasanur forest disease and tick-borne encephalitis viruses by the in silico approach.

Palanisamy, Navaneethan / Akaberi, Dario / Lennerstrand, Johan / Lundkvist, Åke

Pathogens and global health

2018 Volume 112, Issue 4, Page(s) 210–226

Abstract: Alkhumra hemorrhagic fever virus (AHFV), a relatively new member of the Flaviviruses, was discovered in Saudi Arabia 23 years ago. AHFV is classified in the tick-borne encephalitis virus serocomplex, along with the Kyasanur forest disease virus (KFDV) ... ...

Abstract	Alkhumra hemorrhagic fever virus (AHFV), a relatively new member of the Flaviviruses, was discovered in Saudi Arabia 23 years ago. AHFV is classified in the tick-borne encephalitis virus serocomplex, along with the Kyasanur forest disease virus (KFDV) and tick-borne encephalitis virus (TBEV). Currently, very little is known about the pathologies of AHFV. In this study, using the available genome information of AHFV, KFDV and TBEV, we have predicted and compared the following aspects of these viruses: evolution, nucleotide and protein compositions, recombination, codon frequency, substitution rate, N- and O-glycosylation sites, signal peptide and cleavage site, transmembrane region, secondary structure of 5' and 3' UTRs and RNA-RNA interactions. Additionally, we have modeled the 3D protease and RNA-dependent RNA polymerase structures for AHFV, KFDV and TBEV. Recombination analysis showed no evidence of recombination in the AHFV genome with that of either KFDV or TBEV, although single break point analysis showed that nucleotide position 7399 (in the NS4B) is a breakpoint location. AHFV, KFDV and TBEV are very similar in terms of codon frequency, the number of transmembrane regions, properties of the polyprotein, RNA-RNA interaction sequences, NS3 protease and NS5 polymerase structures and 5' UTR structure. Using genome sequences, we showed the similarities between these closely- related viruses on several different areas.
MeSH term(s)	Computational Biology ; Encephalitis Viruses, Tick-Borne/genetics ; Encephalitis Viruses, Tick-Borne/isolation & purification ; Encephalitis, Tick-Borne/virology ; Evolution, Molecular ; Genetic Variation ; Genome, Viral ; Humans ; Nucleic Acid Conformation ; Protein Conformation ; RNA, Viral/chemistry ; RNA, Viral/genetics ; Recombination, Genetic ; Viral Proteins/chemistry ; Viral Proteins/genetics
Chemical Substances	RNA, Viral ; Viral Proteins
Language	English
Publishing date	2018-05-10
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	2625162-0
ISSN	2047-7732 ; 2047-7724
ISSN (online)	2047-7732
ISSN	2047-7724
DOI	10.1080/20477724.2018.1471187
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Article ; Online: Protein backbone flexibility pattern is evolutionarily conserved in the Flaviviridae family: A case of NS3 protease in Flavivirus and Hepacivirus.

Palanisamy, Navaneethan / Akaberi, Dario / Lennerstrand, Johan

Molecular phylogenetics and evolution

2018 Volume 118, Page(s) 58–63

Abstract: Viruses belonging to the Flaviviridae family have been an important health concern for humans, animals and birds alike. No specific treatment is available yet for many of the viral infections caused by the members of this family. Lack of specific drugs ... ...

Abstract	Viruses belonging to the Flaviviridae family have been an important health concern for humans, animals and birds alike. No specific treatment is available yet for many of the viral infections caused by the members of this family. Lack of specific drugs against these viruses is mainly due to lack of protein structure information. It has been known that protein backbone fluctuation pattern is highly conserved in protein pairs with similar folds, in spite of the lack of sequence similarity. We hypothesized that this concept should also hold true for proteins (especially enzymes) of viruses included in different genera of the Flaviviridae family, as we know that the sequence similarity between them is low. Using available NS3 protease crystal structures of the Flaviviridae family, our preliminary results have shown that the Cα (i.e. backbone) fluctuation patterns are highly similar between Flaviviruses and a Hepacivirus (i.e. hepatitis C virus, HCV). This has to be validated further experimentally.
Language	English
Publishing date	2018-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	33610-5
ISSN	1095-9513 ; 1055-7903
ISSN (online)	1095-9513
ISSN	1055-7903
DOI	10.1016/j.ympev.2017.09.015
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Article: Presymptomatic viral shedding and infective ability of SARS-CoV-2; a case report.

Nissen, Karolina / Hagbom, Marie / Krambrich, Janina / Akaberi, Dario / Sharma, Sumit / Ling, Jiaxin / Hoffman, Tove / Svensson, Lennart / Bondeson, Kåre / Salaneck, Erik

Heliyon

2021 Volume 7, Issue 2, Page(s) e06328

Abstract: Possible pre- or asymptomatic transmission has been reported, both from SARS-CoV and from MERS-CoV outbreaks, although this appears to be uncommon. In contrast, during the COVID-19 pandemic, an increasing number of studies and case reports indicate that ... ...

Abstract	Possible pre- or asymptomatic transmission has been reported, both from SARS-CoV and from MERS-CoV outbreaks, although this appears to be uncommon. In contrast, during the COVID-19 pandemic, an increasing number of studies and case reports indicate that pre- or asymptomatic transmission of SARS-CoV-2 is not only possible but also occurs frequently. We report repeated rRT-PCR detection of SARS-CoV-2 in a health care worker and demonstrate infective ability up to three days prior to mild COVID-19 symptoms. rRT-PCR indicated high viral levels approximately three days after exposure. Viral samples collected one and three days prior to symptoms exhibited infectivity on Vero E6 cells, confirmed by detection of double-stranded RNA by immunofluorescence, assessment of cytopathic effect (CPE) and rRT-PCR. SARS-CoV-2 specific IgM and IgG antibodies were detected by day 9 and 15, respectively, after symptom onset. We propose that this provides evidence for potential early presymptomatic transmission of SARS-CoV-2 and that infectivity may be manifest shortly after exposure.
Language	English
Publishing date	2021-02-19
Publishing country	England
Document type	Case Reports
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2021.e06328
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Article ; Online: Targeting the NS2B-NS3 protease of tick-borne encephalitis virus with pan-flaviviral protease inhibitors.

Akaberi, Dario / Båhlström, Amanda / Chinthakindi, Praveen K / Nyman, Tomas / Sandström, Anja / Järhult, Josef D / Palanisamy, Navaneethan / Lundkvist, Åke / Lennerstrand, Johan

Antiviral research

2021 Volume 190, Page(s) 105074

Abstract: Tick-borne encephalitis (TBE) is a severe neurological disorder caused by tick-borne encephalitis virus (TBEV), a member of the Flavivirus genus. Currently, two vaccines are available in Europe against TBEV. However, TBE cases have been rising in Sweden ... ...

Abstract	Tick-borne encephalitis (TBE) is a severe neurological disorder caused by tick-borne encephalitis virus (TBEV), a member of the Flavivirus genus. Currently, two vaccines are available in Europe against TBEV. However, TBE cases have been rising in Sweden for the past twenty years, and thousands of cases are reported in Europe, emphasizing the need for antiviral treatments against this virus. The NS2B-NS3 protease is essential for flaviviral life cycle and has been studied as a target for the design of inhibitors against several well-known flaviviruses, but not TBEV. In the present study, Compound 86, a known tripeptidic inhibitor of dengue (DENV), West Nile (WNV) and Zika (ZIKV) proteases, was predicted to be active against TBEV protease using a combination of in silico techniques. Further, Compound 86 was found to inhibit recombinant TBEV protease with an IC
MeSH term(s)	Antiviral Agents/pharmacology ; Computer Simulation ; Encephalitis Viruses, Tick-Borne/drug effects ; Encephalitis Viruses, Tick-Borne/enzymology ; Encephalitis, Tick-Borne/drug therapy ; Encephalitis, Tick-Borne/virology ; Molecular Docking Simulation ; Peptide Hydrolases/chemistry ; Protease Inhibitors/classification ; Protease Inhibitors/metabolism ; Protease Inhibitors/pharmacology ; RNA Helicases/antagonists & inhibitors ; RNA Helicases/metabolism ; Serine Endopeptidases/metabolism ; Viral Nonstructural Proteins/antagonists & inhibitors ; Viral Nonstructural Proteins/metabolism
Chemical Substances	Antiviral Agents ; NS2B protein, flavivirus ; NS3 protein, flavivirus ; Protease Inhibitors ; Viral Nonstructural Proteins ; Peptide Hydrolases (EC 3.4.-) ; Serine Endopeptidases (EC 3.4.21.-) ; RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2021-04-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2021.105074
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Article: Corrigendum to "Presymptomatic viral shedding and infective ability of SARS-CoV-2; a case report" [Heliyon 7, (2), (February 2021), Article e06328].

Nissen, Karolina / Hagbom, Marie / Krambrich, Janina / Akaberi, Dario / Sharma, Sumit / Ling, Jiaxin / Hoffman, Tove / Lundkvist, Åke / Svensson, Lennart / Bondeson, Kåre / Salaneck, Erik

Heliyon

2022 Volume 8, Issue 2, Page(s) e08906

Abstract: This corrects the article DOI: 10.1016/j.heliyon.2021.e06328.]. ...

Abstract	[This corrects the article DOI: 10.1016/j.heliyon.2021.e06328.].
Language	English
Publishing date	2022-02-05
Publishing country	England
Document type	Published Erratum
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2022.e08906
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Article ; Online: Long-distance airborne dispersal of SARS-CoV-2 in COVID-19 wards.

Nissen, Karolina / Krambrich, Janina / Akaberi, Dario / Hoffman, Tove / Ling, Jiaxin / Lundkvist, Åke / Svensson, Lennart / Salaneck, Erik

Scientific reports

2020 Volume 10, Issue 1, Page(s) 19589

Abstract: Evidence suggests that SARS-CoV-2, as well as other coronaviruses, can be dispersed and potentially transmitted by aerosols directly or via ventilation systems. We therefore investigated ventilation openings in one COVID-19 ward and central ducts that ... ...

Abstract	Evidence suggests that SARS-CoV-2, as well as other coronaviruses, can be dispersed and potentially transmitted by aerosols directly or via ventilation systems. We therefore investigated ventilation openings in one COVID-19 ward and central ducts that expel indoor air from three COVID-19 wards at Uppsala University Hospital, Sweden, during April and May 2020. Swab samples were taken from individual ceiling ventilation openings and surfaces in central ducts. Samples were subsequently subjected to rRT-PCR targeting the N and E genes of SARS-CoV-2. Central ventilation HEPA filters, located several stories above the wards, were removed and portions analyzed in the same manner. In two subsequent samplings, SARS-CoV-2 N and E genes were detected in seven and four out of 19 room vents, respectively. Central ventilation HEPA exhaust filters from the ward were found positive for both genes in three samples. Corresponding filters from two other, adjacent COVID-19 wards were also found positive. Infective ability of the samples was assessed by inoculation of susceptible cell cultures but could not be determined in these experiments. Detection of SARS-CoV-2 in central ventilation systems, distant from patient areas, indicate that virus can be transported long distances and that droplet transmission alone cannot reasonably explain this, especially considering the relatively low air change rates in these wards. Airborne transmission of SARS-CoV-2 must be taken into consideration for preventive measures.
MeSH term(s)	Aerosols ; Animals ; Betacoronavirus/genetics ; Betacoronavirus/physiology ; COVID-19 ; Chlorocebus aethiops ; Coronavirus Infections/epidemiology ; Coronavirus Infections/transmission ; Coronavirus Infections/virology ; Filtration ; Hospitals ; Pandemics/prevention & control ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/transmission ; Pneumonia, Viral/virology ; RNA, Viral/analysis ; SARS-CoV-2 ; Ventilation ; Vero Cells
Chemical Substances	Aerosols ; RNA, Viral
Keywords	covid19
Language	English
Publishing date	2020-11-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-76442-2
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Article: Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2.

Hoffman, Tove / Nissen, Karolina / Krambrich, Janina / Rönnberg, Bengt / Akaberi, Dario / Esmaeilzadeh, Mouna / Salaneck, Erik / Lindahl, Johanna / Lundkvist, Åke

Infection ecology & epidemiology

2020 Volume 10, Issue 1, Page(s) 1754538

Abstract: COVID-19 is the most rapidly growing pandemic in modern time, and the need for serological testing is most urgent. Although the diagnostics of acute patients by RT-PCR is both efficient and specific, we are also crucially in need of serological tools for ...

Abstract	COVID-19 is the most rapidly growing pandemic in modern time, and the need for serological testing is most urgent. Although the diagnostics of acute patients by RT-PCR is both efficient and specific, we are also crucially in need of serological tools for investigating antibody responses and assessing individual and potential herd immunity. We evaluated a commercially available test developed for rapid (within 15 minutes) detection of SARS-CoV-2-specific IgM and IgG by 29 PCR-confirmed COVID-19 cases and 124 negative controls. The results revealed a sensitivity of 69% and 93.1% for IgM and IgG, respectively, based solely on PCR-positivity due to the absence of a serological gold standard. The assay specificities were shown to be 100% for IgM and 99.2% for IgG. This indicates that the test is suitable for assessing previous virus exposure, although negative results may be unreliable during the first weeks after infection. More detailed studies on antibody responses during and post infection are urgently needed.
Keywords	covid19
Language	English
Publishing date	2020-04-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2627673-2
ISSN	2000-8686
ISSN	2000-8686
DOI	10.1080/20008686.2020.1754538
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Article ; Online: Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro.

Akaberi, Dario / Krambrich, Janina / Ling, Jiaxin / Luni, Chen / Hedenstierna, Göran / Järhult, Josef D / Lennerstrand, Johan / Lundkvist, Åke

Redox biology

2020 Volume 37, Page(s) 101734

Abstract: The ongoing SARS-CoV-2 pandemic is a global public health emergency posing a high burden on nations' health care systems and economies. Despite the great effort put in the development of vaccines and specific treatments, no prophylaxis or effective ... ...

Abstract	The ongoing SARS-CoV-2 pandemic is a global public health emergency posing a high burden on nations' health care systems and economies. Despite the great effort put in the development of vaccines and specific treatments, no prophylaxis or effective therapeutics are currently available. Nitric oxide (NO) is a broad-spectrum antimicrobial and a potent vasodilator that has proved to be effective in reducing SARS-CoV replication and hypoxia in patients with severe acute respiratory syndrome. Given the potential of NO as treatment for SARS-CoV-2 infection, we have evaluated the in vitro antiviral effect of NO on SARS-CoV-2 replication. The NO-donor S-nitroso-N-acetylpenicillamine (SNAP) had a dose dependent inhibitory effect on SARS-CoV-2 replication, while the non S-nitrosated NAP was not active, as expected. Although the viral replication was not completely abolished (at 200 μM and 400 μM), SNAP delayed or completely prevented the development of viral cytopathic effect in treated cells, and the observed protective effect correlated with the level of inhibition of the viral replication. The capacity of the NO released from SNAP to covalently bind and inhibit SARS-CoV-2 3CL recombinant protease in vitro was also tested. The observed reduction in SARS-CoV-2 protease activity was consistent with S-nitrosation of the enzyme active site cysteine.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Catalytic Domain/drug effects ; Chlorocebus aethiops ; Coronavirus 3C Proteases/antagonists & inhibitors ; Coronavirus 3C Proteases/metabolism ; Humans ; Models, Molecular ; Nitric Oxide/pharmacology ; Nitric Oxide Donors/pharmacology ; S-Nitroso-N-Acetylpenicillamine/pharmacology ; SARS-CoV-2/drug effects ; SARS-CoV-2/enzymology ; SARS-CoV-2/physiology ; Vero Cells ; Viral Protease Inhibitors/pharmacology ; Virus Replication/drug effects ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; Nitric Oxide Donors ; Viral Protease Inhibitors ; Nitric Oxide (31C4KY9ESH) ; S-Nitroso-N-Acetylpenicillamine (79032-48-7) ; 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28)
Keywords	covid19
Language	English
Publishing date	2020-09-21
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2020.101734
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