In vitro and in vivo studies of deglycosylated chimeric porcine reproductive and respiratory syndrome virus as a vaccine candidate and its realistic revenue impact at commercial pig production level

Hydroxychloroquine and chloroquine are medications that have been used for a long time. Their most common use is for the treatment and prophylaxis of malaria. However, these antimalarial drugs are known to also have anti-inflammatory and antiviral effects and are used for several chronic diseases such as systemic lupus erythematosus with low adverse effects. The antiviral action of hydroxychloroquine and chloroquine has been a point of interest to different researchers due to its mechanism of action. Several in vitro studies have proven their effectiveness on severe acute respiratory syndrome virus and currently both in vitro and in vivo studies have been conducted on 2019 novel coronavirus (covid-19). The purpose of this article is to review the history and mechanism of actions of these drugs and the potential use they can have on the current covid-19 pandemic.

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Platycodin D Suppresses Type 2 Porcine Reproductive and Respiratory Syndrome Virus In Primary and Established Cell Lines

Viruses ◽

10.3390/v10110657 ◽

2018 ◽

Vol 10 (11) ◽

pp. 657 ◽

Cited By ~ 8

Author(s):

Mingxin Zhang ◽

Taofeng Du ◽

Feixiang Long ◽

Xia Yang ◽

Yankuo Sun ◽

...

Keyword(s):

Virus Production ◽

In Vivo Studies ◽

Progeny Virus ◽

Respiratory Syndrome Virus ◽

Dependent Manner ◽

Triterpenoid Saponins ◽

Platycodin D

Porcine reproductive and respiratory syndrome virus (PRRSV) is a continuous threat to the pork industry as it continues to cause significant economic loss worldwide. Currently, vaccination strategies provide very limited protection against PRRSV transmission. Consequently, there is an urgent need to develop new antiviral strategies. Platycodin D (PD) is one of the major bioactive triterpenoid saponins derived from Platycodon grandiflorum, a traditional Chinese medicine used as an expectorant for pulmonary diseases and a remedy for respiratory disorders. Here, we demonstrate that PD exhibits potent activity against PRRSV infection in Marc-145 cells and primary porcine alveolar macrophages. PD exhibited broad-spectrum inhibitory activities in vitro against high pathogenic type 2 PRRSV GD-HD strain and GD-XH strain as well as classical CH-1a and VR2332 strains. PD at concentrations ranging 1–4 μM significantly inhibited PRRSV RNA synthesis, viral protein expression and progeny virus production in a dose-dependent manner. EC50 values of PD against four tested PRRSV strains infection in Marc-145 cells ranged from 0.74 to 1.76 μM. Mechanistically, PD inhibited PRRSV replication by directly interacting with virions therefore affecting multiple stages of the virus life cycle, including viral entry and progeny virus release. In addition, PD decreased PRRSV- and LPS-induced cytokine (IFN-α, IFN-β, IL-1α, IL-6, IL-8 and TNF-α) production in PAMs. Altogether, our findings suggested that PD is a potent inhibitor of PPRSV infection in vitro. However, further in vivo studies are necessary to confirm PD as a potential novel and effective PPRSV inhibitor in swine.

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Attenuation and Immunogenicity of a Live High Pathogenic PRRSV Vaccine Candidate with a 32-Amino Acid Deletion in the nsp2 Protein

Journal of Immunology Research ◽

10.1155/2014/810523 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Wenhui Lu ◽

Baoli Sun ◽

Jianyue Mo ◽

Xiduo Zeng ◽

Guanqun Zhang ◽

...

Keyword(s):

Amino Acid ◽

Vaccine Candidate ◽

Clinical Signs ◽

Respiratory Syndrome Virus ◽

Amino Acid Deletion ◽

Lethal Challenge ◽

Nsp2 Gene ◽

Amino Acid Mutations

A porcine reproductive and respiratory syndrome virus (PRRSV) QY1 was serially passed on Marc-145 cells. Virulence of different intermediate derivatives of QY1 (P5, P60, P80, and P100) were determined. The study found that QY1 had been gradually attenuated during the in vitro process. Pathogenicity study showed that pigs inoculated with QY1 P100 and P80 did not develop any significant PRRS clinic symptoms. However, mild-to-moderate clinical signs and acute HP-PRRSV symptoms of infection were observed in pigs inoculated with QY1 P60 and P5, respectively. Furthermore, we determined the whole genome sequences of these four intermediate viruses. The results showed that after 100 passages, compared to QY1 P5, a total of 32 amino acid mutations were found. Moreover, there were one nucleotide deletion and a unique 34-amino acid deletion found at 5′UTR and in nsp2 gene during the attenuation process, respectively. Such deletions were genetically stable in vivo. Following PRRSV experimental challenge, pigs inoculated with a single dose of QY1 P100 developed no significant clinic symptoms and well tolerated lethal challenge, while QY1 P80 group still developed mild fever in the clinic trial after challenge. Thus, we concluded that QY1 P100 was a promising and highly attenuated PRRSV vaccine candidate.

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Regulation of vascular endothelial growth factor expression in human endometrium by steroids and hypoxia: In vitro and in vivo studies

Journal of the Society for Gynecologic Investigation ◽

10.1016/s1071-5576(97)86195-3 ◽

1998 ◽

Vol 5 (1) ◽

pp. 69A-69A

Author(s):

A SHARKEY ◽

D CHARNOCKJONES ◽

K DAY ◽

H SOWTER ◽

L SVENSSON ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Human Endometrium ◽

In Vivo Studies ◽

Vascular Endothelial ◽

Factor Expression ◽

Growth Factor Expression ◽

Endothelial Growth Factor

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In vitro and in vivo studies of new cationic Zn(II)‐benzonaphthoporphyrazines as photosensitizers for PDT

Journal of Porphyrins and Phthalocyanines ◽

10.1002/jpp.373.abs ◽

2001 ◽

Vol 5 (8) ◽

pp. 645-651

Author(s):

M. Peeva ◽

M. Shopova ◽

U. Michelsen ◽

D. Wöhrle ◽

G. Petrov ◽

...

Keyword(s):

In Vivo Studies

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Effect of caffeine on theophyliine on cerebral blood flow response to brain activation: In vitro and in vivo studies

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0198 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S198-S198

Author(s):

Joseph R Meno ◽

Thien-son K Nguyen ◽

Elise M Jensen ◽

G Alexander West ◽

Leonid Groysman ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Brain Activation ◽

In Vivo Studies ◽

Blood Flow Response ◽

Flow Response

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Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648988 ◽

1994 ◽

Vol 72 (06) ◽

pp. 942-946 ◽

Cited By ~ 20

Author(s):

Raffaele Landolfi ◽

Erica De Candia ◽

Bianca Rocca ◽

Giovanni Ciabattoni ◽

Armando Antinori ◽

...

Keyword(s):

Molecular Weight ◽

Unfractionated Heparin ◽

Low Molecular Weight Heparin ◽

Primary Source ◽

In Vivo Studies ◽

Low Molecular Weight ◽

Heparin Administration ◽

To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

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