A Comparative Analysis of the Spanish Flu 1918 and COVID-19 Pandemics

Two devastating pandemics, the Spanish Flu and COVID-19, emerged globally in 1918 from America and 2019 from China, respectively. Influenza virus A H1N1, which caused Spanish Flu and SARS-CoV2, which caused COVID-19, belong to different virus family and bear different structure, genomic organization and pathogenicity. However, the trajectory of the current outbreak of COVID-19 depicts a similar picture of the Spanish Flu outbreak. Estimates suggest that ~500 million infected cases and ~50 million deaths occurred globally from 1918-1919 due to the H1N1 virus. While SARS-CoV2 accounted for ~2 million cases and 130,885 deaths just within three and a half months, and the number is still increasing. To contain the spread of COVID-19 and to prevent the situation which happened a century back, it becomes essential to examine and correlate these pandemics in terms of their origin, epidemiology and clinical scenario. The strategies tailored to control the Spanish Flu pandemic may help to contain the current pandemic within time.

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A comparative analysis of virucidal efficiency of biocide agents

Voprosy Virusologii ◽

10.18821/0507-4088-2017-62-1-41-45 ◽

2017 ◽

Vol 62 (1) ◽

pp. 41-45

Author(s):

N. N. Nosik ◽

D. N. Nosik ◽

A. I. Chizhov

Keyword(s):

Influenza Virus ◽

Comparative Analysis ◽

Hepatitis C ◽

Viral Hepatitis ◽

Virucidal Activity ◽

Enveloped Viruses ◽

Influenza Virus A ◽

Viral Hepatitis C ◽

Ammonium Compounds ◽

Inactivation Of Bacteria

The main groups of biocide agents used for inactivation of bacteria and viruses were studied for their virucidal activity against enveloped (HIV, viral hepatitis C, influenza virus A) and non-enveloped viruses (poliovirus, adenovirus). Their efficiency was analyzed. Quarterly ammonium compounds (QAC) themselves are not able to properly inactivate non-enveloped viruses. However, they can be successfully applied in combination with other biocides (guanidines, aldehydes). Effective composition of QAC with amines and guanidines provided inactivation of viruses (4.0 lgTCID50) in concentrations of 0.166-0.280% for non-enveloped viruses and 0.080-00.185% for enveloped viruses. The combination of QAC with aldehydes is especially effective (0.04-0.64% for non-enveloped viruses). The virucidal efficiency does not directly depend on the QAC concentration in the chemical disinfectants.

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Experimental Infection of Pigs with the Human 1918 Pandemic Influenza Virus

Journal of Virology ◽

10.1128/jvi.02399-08 ◽

2009 ◽

Vol 83 (9) ◽

pp. 4287-4296 ◽

Cited By ~ 45

Author(s):

Hana M. Weingartl ◽

Randy A. Albrecht ◽

Kelly M. Lager ◽

Shawn Babiuk ◽

Peter Marszal ◽

...

Keyword(s):

Influenza Virus ◽

Pandemic Influenza ◽

H1n1 Virus ◽

Swine Influenza ◽

H1n1 Influenza ◽

Influenza Viruses ◽

H1n1 Influenza Virus ◽

Severe Respiratory Distress ◽

Pandemic H1n1 Influenza ◽

Spanish Flu

ABSTRACT Swine influenza was first recognized as a disease entity during the 1918 “Spanish flu” pandemic. The aim of this work was to determine the virulence of a plasmid-derived human 1918 pandemic H1N1 influenza virus (reconstructed 1918, or 1918/rec, virus) in swine using a plasmid-derived A/swine/Iowa/15/1930 H1N1 virus (1930/rec virus), representing the first isolated influenza virus, as a reference. Four-week-old piglets were inoculated intratracheally with either the 1930/rec or the 1918/rec virus or intranasally with the 1918/rec virus. A transient increase in temperature and mild respiratory signs developed postinoculation in all virus-inoculated groups. In contrast to other mammalian hosts (mice, ferrets, and macaques) where infection with the 1918/rec virus was lethal, the pigs did not develop severe respiratory distress or become moribund. Virus titers in the lower respiratory tract as well as macro- and microscopic lesions at 3 and 5 days postinfection (dpi) were comparable between the 1930/rec and 1918/rec virus-inoculated animals. In contrast to the 1930/rec virus-infected animals, at 7 dpi prominent lung lesions were present in only the 1918/rec virus-infected animals, and all the piglets developed antibodies at 7 dpi. Presented data support the hypothesis that the 1918 pandemic influenza virus was able to infect and replicate in swine, causing a respiratory disease, and that the virus was likely introduced into the pig population during the 1918 pandemic, resulting in the current lineage of the classical H1N1 swine influenza viruses.

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Phylogenetic analysis of hemagglutinin (HA) gene of the novel avian influenza virus A/H7N9

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2013.00595 ◽

2013 ◽

Vol 33 (6) ◽

pp. 595-601

Author(s):

Wei GUAN ◽

Zi-xiong LI ◽

Ji LIN ◽

Yi-fang HAN ◽

Tong SU ◽

...

Keyword(s):

Phylogenetic Analysis ◽

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

The Novel ◽

Influenza Virus A ◽

Ha Gene

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1-Acyl-3-cyclooctylguanidines

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19801595 ◽

1980 ◽

Vol 45 (5) ◽

pp. 1595-1600 ◽

Cited By ~ 3

Author(s):

Jaroslav Sluka ◽

František Šmejkal ◽

Zdeněk Buděšínský

Keyword(s):

Influenza Virus ◽

Herpes Simplex ◽

Methyl Esters ◽

Antiviral Effect ◽

Influenza Virus A

On recation of cyclooctylamine with the sulfate of S-methylisothiourea cyclooctylguanidine was formed which was acylated with the methyl esters of 5-halogeno- and 3,5-dihalogeno-2-alkoxybenzoic acids. The 1-acyl-3-cyclooctylguanidine I-XVII formed were tested for their antiviral effect against the influenza virus A/NWS, A-PR8 and A2 Singapore, and further against the viruses NDV, herpes 2, vaccinia and WEE. In the in vivo test against the influenza virus A2 Singapore and herpes simplex 1-(5-bromo-2-dodecyloxybenzoyl)-3-cyclooctylguanidine is more active and less toxic than cyclooctylamine and 1-cyclooctylguanidine.

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Recent Avian Influenza Virus A/H5N1 Evolution in Vaccinated and Unvaccinated Poultry from Farms in Southern Vietnam, January-March 2010

Transboundary and Emerging Diseases ◽

10.1111/j.1865-1682.2011.01229.x ◽

2011 ◽

Vol 58 (6) ◽

pp. 537-543 ◽

Cited By ~ 17

Author(s):

N. T. Long ◽

T. T. Thanh ◽

H. R. van Doorn ◽

P. P. Vu ◽

P. T. Dung ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Influenza Virus A ◽

Southern Vietnam

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Synthesis and Antiviral Evaluation of Nucleoside Analogues Bearing One Pyrimidine Moiety and Two D-Ribofuranosyl Residues

Molecules ◽

10.3390/molecules26123678 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3678

Author(s):

Olga V. Andreeva ◽

Bulat F. Garifullin ◽

Vladimir V. Zarubaev ◽

Alexander V. Slita ◽

Iana L. Yesaulkova ◽

...

Keyword(s):

Influenza Virus ◽

Antiviral Activity ◽

Theoretical Calculations ◽

Nucleoside Analogs ◽

Coxsackievirus B3 ◽

Nucleoside Analogues ◽

Moderate Activity ◽

Coat Proteins ◽

Influenza Virus A ◽

Ic50 Values

A series of 1,2,3-triazolyl nucleoside analogues in which 1,2,3-triazol-4-yl-β-d-ribofuranosyl fragments are attached via polymethylene linkers to both nitrogen atoms of the heterocycle moiety (uracil, 6-methyluracil, thymine, quinazoline-2,4-dione, alloxazine) or to the C-5 and N-3 atoms of the 6-methyluracil moiety was synthesized. All compounds synthesized were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1) and coxsackievirus B3. Antiviral assays revealed three compounds, 2i, 5i, 11c, which showed moderate activity against influenza virus A H1N1 with IC50 values of 57.5 µM, 24.3 µM, and 29.2 µM, respectively. In the first two nucleoside analogues, 1,2,3-triazol-4-yl-β-d-ribofuranosyl fragments are attached via butylene linkers to N-1 and N-3 atoms of the heterocycle moiety (6-methyluracil and alloxazine, respectively). In nucleoside analogue 11c, two 1,2,3-triazol-4-yl-2′,3′,5′-tri-O-acetyl-β-d-ribofuranose fragments are attached via propylene linkers to the C-5 and N-3 atoms of the 6-methyluracil moiety. Almost all synthesized 1,2,3-triazolyl nucleoside analogues showed no antiviral activity against the coxsackie B3 virus. Two exceptions are 1,2,3-triazolyl nucleoside analogs 2f and 5f, in which 1,2,3-triazol-4-yl-2′,3′,5′-tri-O-acetyl-β-d-ribofuranose fragments are attached to the C-5 and N-3 atoms of the heterocycle moiety (6-methyluracil and alloxazine respectively). These compounds exhibited high antiviral potency against the coxsackie B3 virus with IC50 values of 12.4 and 11.3 µM, respectively, although both were inactive against influenza virus A H1N1. According to theoretical calculations, the antiviral activity of the 1,2,3-triazolyl nucleoside analogues 2i, 5i, and 11c against the H1N1 (A/PR/8/34) influenza virus can be explained by their influence on the functioning of the polymerase acidic protein (PA) of RNA-dependent RNA polymerase (RdRp). As to the antiviral activity of nucleoside analogs 2f and 5f against coxsackievirus B3, it can be explained by their interaction with the coat proteins VP1 and VP2.

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Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection

Vaccines ◽

10.3390/vaccines9070793 ◽

2021 ◽

Vol 9 (7) ◽

pp. 793

Author(s):

Ying Huang ◽

Monique S. França ◽

James D. Allen ◽

Hua Shi ◽

Ted M. Ross

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Immune Responses ◽

H1n1 Virus ◽

Influenza Virus Infection ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Next Generation ◽

Wild Type ◽

Influenza A H1n1

Vaccination is the best way to prevent influenza virus infections, but the diversity of antigenically distinct isolates is a persistent challenge for vaccine development. In order to conquer the antigenic variability and improve influenza virus vaccine efficacy, our research group has developed computationally optimized broadly reactive antigens (COBRAs) in the form of recombinant hemagglutinins (rHAs) to elicit broader immune responses. However, previous COBRA H1N1 vaccines do not elicit immune responses that neutralize H1N1 virus strains in circulation during the recent years. In order to update our COBRA vaccine, two new candidate COBRA HA vaccines, Y2 and Y4, were generated using a new seasonal-based COBRA methodology derived from H1N1 isolates that circulated during 2013–2019. In this study, the effectiveness of COBRA Y2 and Y4 vaccines were evaluated in mice, and the elicited immune responses were compared to those generated by historical H1 COBRA HA and wild-type H1N1 HA vaccines. Mice vaccinated with the next generation COBRA HA vaccines effectively protected against morbidity and mortality after infection with H1N1 influenza viruses. The antibodies elicited by the COBRA HA vaccines were highly cross-reactive with influenza A (H1N1) pdm09-like viruses isolated from 2009 to 2021, especially with the most recent circulating viruses from 2019 to 2021. Furthermore, viral loads in lungs of mice vaccinated with Y2 and Y4 were dramatically reduced to low or undetectable levels, resulting in minimal lung injury compared to wild-type HA vaccines following H1N1 influenza virus infection.

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Exacerbation of Influenza Virus Infections in Mice by Intranasal Treatments and Implications for Evaluation of Antiviral Drugs

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01664-12 ◽

2012 ◽

Vol 56 (12) ◽

pp. 6328-6333 ◽

Cited By ~ 15

Author(s):

Donald F. Smee ◽

Mark von Itzstein ◽

Beenu Bhatt ◽

E. Bart Tarbet

Keyword(s):

Influenza Virus ◽

Influenza A ◽

H1n1 Virus ◽

Antiviral Agent ◽

Virus Production ◽

Lung Pathology ◽

Virus Infections ◽

Challenge Dose ◽

Virus Challenge ◽

Time To Death

ABSTRACTCompounds lacking oral activity may be delivered intranasally to treat influenza virus infections in mice. However, intranasal treatments greatly enhance the virulence of such virus infections. This can be partially compensated for by giving reduced virus challenge doses. These can be 100- to 1,000-fold lower than infections without such treatment and still cause equivalent mortality. We found that intranasal liquid treatments facilitate virus production (probably through enhanced virus spread) and that lung pneumonia was delayed by only 2 days relative to a 1,000-fold higher virus challenge dose not accompanied by intranasal treatments. In one study, zanamivir was 90 to 100% effective at 10 mg/kg/day by oral, intraperitoneal, and intramuscular routes against influenza A/California/04/2009 (H1N1) virus in mice. However, the same compound administered intranasally at 20 mg/kg/day for 5 days gave no protection from death although the time to death was significantly delayed. A related compound, Neu5Ac2en (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid), was ineffective at 100 mg/kg/day. Intranasal zanamivir and Neu5Ac2en were 70 to 100% protective against influenza A/NWS/33 (H1N1) virus infections at 0.1 to 10 and 30 to 100 mg/kg/day, respectively. Somewhat more difficult to treat was A/Victoria/3/75 virus that required 10 mg/kg/day of zanamivir to achieve full protection. These results illustrate that treatment of influenza virus infections by the intranasal route requires consideration of both virus challenge dose and virus strain in order to avoid compromising the effectiveness of a potentially useful antiviral agent. In addition, the intranasal treatments were shown to facilitate virus replication and promote lung pathology.

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