Multiple organ failure might be an indication for prophylactic antifungal therapy in acute pancreatitis

Ning, Caihong; Zhu, Song; Zhou, Shuyi; Lin, Chia-Yen; Li, Jiarong; Cao, Xiaodan; Bonsu, Abdul Aziz F K; Shen, Dingcheng; Li, Yong; Huang, Gengwen

doi:10.1007/s15010-021-01625-6

Cited by 9 publications

(9 citation statements)

References 10 publications

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“…To date, several nucleotide analogs and non-nucleotide drugs have been found to inhibit the viral RNA replication and transcription. Remdesivir, the only FDA-approved drug for COVID-19 treatment [ 105 ], is a pro-drug containing a C1′-cyano substituted adenine and requires in vivo phosphorylation to form the active drug remdesivir triphosphate (RTP). After RTP is incorporated into a growing RNA product, it stalls RdRP because of steric clashes between the C1′-cyano group and Ser 861 (S861) (Fig.…”

Section: Structures Of Rtc and Rtc Inhibitorsmentioning

confidence: 99%

“…For example, how nsp12 binds an incoming NTP and incorporates it into RNA; how nsp13 helicase facilitates RNA synthesis and cap formation; how the RNAs are capped by NiRAN; and whether other viral and host factors are involved in RTC formation and RNA synthesis is still unknown. To date, the multi-subunit RTC complex has been successfully drugged [ 99 , 101 , 105 ]. But all viral encoded proteins are potential targets for inhibition of SARS-CoV-2 infection.…”

Section: Remarks and Perspectivesmentioning

confidence: 99%

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SARS-CoV-2: from its discovery to genome structure, transcription, and replication

Tian²,

et al. 2021

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SARS-CoV-2 is an extremely contagious respiratory virus causing adult atypical pneumonia COVID-19 with severe acute respiratory syndrome (SARS). SARS-CoV-2 has a single-stranded, positive-sense RNA (+RNA) genome of ~ 29.9 kb and exhibits significant genetic shift from different isolates. After entering the susceptible cells expressing both ACE2 and TMPRSS2, the SARS-CoV-2 genome directly functions as an mRNA to translate two polyproteins from the ORF1a and ORF1b region, which are cleaved by two viral proteases into sixteen non-structural proteins (nsp1-16) to initiate viral genome replication and transcription. The SARS-CoV-2 genome also encodes four structural (S, E, M and N) and up to six accessory (3a, 6, 7a, 7b, 8, and 9b) proteins, but their translation requires newly synthesized individual subgenomic RNAs (sgRNA) in the infected cells. Synthesis of the full-length viral genomic RNA (gRNA) and sgRNAs are conducted inside double-membrane vesicles (DMVs) by the viral replication and transcription complex (RTC), which comprises nsp7, nsp8, nsp9, nsp12, nsp13 and a short RNA primer. To produce sgRNAs, RTC starts RNA synthesis from the highly structured gRNA 3' end and switches template at various transcription regulatory sequence (TRSB) sites along the gRNA body probably mediated by a long-distance RNA–RNA interaction. The TRS motif in the gRNA 5' leader (TRSL) is responsible for the RNA–RNA interaction with the TRSB upstream of each ORF and skipping of the viral genome in between them to produce individual sgRNAs. Abundance of individual sgRNAs and viral gRNA synthesized in the infected cells depend on the location and read-through efficiency of each TRSB. Although more studies are needed, the unprecedented COVID-19 pandemic has taught the world a painful lesson that is to invest and proactively prepare future emergence of other types of coronaviruses and any other possible biological horrors.

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Section: Structures Of Rtc and Rtc Inhibitorsmentioning

confidence: 99%

Section: Remarks and Perspectivesmentioning

confidence: 99%

SARS-CoV-2: from its discovery to genome structure, transcription, and replication

Tian²,

et al. 2021

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“…Indeed, there are several reports showing the association between SAP and fungal infection (Kochhar et al, 2011;Rasch et al, 2018;Singh et al, 2021). As shown in Table 1, the rates of fungal infection as assessed by isolation of blood or pancreatic tissues or by the presence of b-d-glucan antigenemia are highly variable ranging from 7.6% to 46.3% in patients with AP (Kochhar et al, 2009;Vege et al, 2009;Ignatavicius et al, 2012;Werge et al, 2016;Mandal et al, 2017;Rasch et al, 2018;Ning et al, 2021). Such highly variable results can be explained by the difference of severity in patients with AP; the incidence of pancreatic fungal infection is parallel to the severity of AP.…”

Section: Link Between Fungal Infection and Human Sapmentioning

confidence: 99%

“…As for the efficacy of anti-fungal therapy consisting of amphotericin B and/or fluconazole for SAP, four studies started anti-fungal therapy after isolation of fungi (Kochhar et al, 2009;Werge et al, 2016;Rasch et al, 2018;Ning et al, 2021). On the other hand, antifungal therapy was initiated prophylactically in one study in which prophylactic antifungal therapy was performed in 19 cases due to b-D-glucan positivity in the serum (Vege et al, 2009) despite without fungal detection in culture tests.…”

Section: Anti-fungal Therapy In Sapmentioning

confidence: 99%

“…However, Tissot et al reported superiority of b-D-glucan detection for the diagnosis of intraabdominal Candida infection as compared with conventional culture methods (Tissot et al, 2013). Alternatively, the presence of multiple organ failure might be an indication for prophylactic anti-fungal therapy (Ning et al, 2021). Further studies addressing the efficacy and timing of anti-fungal therapy for SAP are absolutely required.…”

Section: Anti-fungal Therapy In Sapmentioning

confidence: 99%

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Pancreatic colonization of fungi in the development of severe acute pancreatitis

Otsuka

Kamata

Minaga

et al. 2022

Front. Cell. Infect. Microbiol.

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Acute pancreatitis is a common emergent disorder, a significant population of which develops the life-threatening condition, called severe acute pancreatitis (SAP). It is generally accepted that bacterial infection is associated with the development and persistence of SAP. In addition to bacterial infection, recent clinical studies disclosed a high incidence of fungal infection in patients with SAP. Moreover, SAP patients with fungal infection exhibit a higher mortality rate than those without infection. Although these clinical studies support pathogenic roles played by fungal infection in SAP, beneficial effects of prophylactic anti-fungal therapy on SAP have not been proved. Here we summarize recent clinical findings as to the relationship between fungal infection and the development of SAP. In addition, we discuss molecular mechanisms accounting for the development of SAP in the presence of fungal infection.

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Antifungal prophylaxis and pre-emptive therapy: When and how?

Sprute

Nacov

Neofytos

et al. 2023

Molecular Aspects of Medicine

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Multiple organ failure might be an indication for prophylactic antifungal therapy in acute pancreatitis

Cited by 9 publications

References 10 publications

SARS-CoV-2: from its discovery to genome structure, transcription, and replication

SARS-CoV-2: from its discovery to genome structure, transcription, and replication

Pancreatic colonization of fungi in the development of severe acute pancreatitis

Antifungal prophylaxis and pre-emptive therapy: When and how?

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