Numb-associated kinases are required for SARS-CoV-2 infection and are cellular targets for antiviral strategies

Karim, Marwah; Saul, Sirle; Ghita, Luca; Sahoo, Malaya K.; Ye, Chengjin; Bhalla, Nishank; Lo, Chieh Wen; Jin, Jing; Park, Jun-Gyu; Martínez-Gualda, Belén; East, Michael P.; Johnson, Gary L.; Pinsky, Benjamin A.; Martínez-Sobrido, Luis; Asquith, Christopher R. M.; Narayanan, Aarthi; Jonghe, Steven De; Einav, Shirit

doi:10.1016/j.antiviral.2022.105367

Cited by 27 publications

(40 citation statements)

References 59 publications

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“…Previous study has suggested that synthetic peptides corresponding to the CT of the S protein inhibit SARS-CoV-2 infection by blunting the interaction between the S protein and the N protein ( Park et al, 2021 ). Moreover, inhibition of the Numb-associated kinases, which regulates intracellular membrane trafficking, effectively suppressed SARS-CoV-2 infection ( Karim et al, 2022 ; Xiang et al, 2022b ). Our results provided data that knocking down the expression of APRC3, SCAMP3, and TUBB8 significantly suppresses the assembly of the single-round infectious SARS-CoV-2 virions, suggesting that their important roles on SARS-CoV-2 infection or assembly ( Fig.…”

Section: Discussionmentioning

confidence: 99%

A new intracellular targeting motif in the cytoplasmic tail of the spike protein may act as a target to inhibit SARS-CoV-2 assembly

Tang

Mei

et al. 2023

Antiviral Research

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Section: Discussionmentioning

confidence: 99%

A new intracellular targeting motif in the cytoplasmic tail of the spike protein may act as a target to inhibit SARS-CoV-2 assembly

Tang

Mei

et al. 2023

Antiviral Research

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“…A previously identified AAK1 inhibitor (compound 1) with demonstrated antiviral activity against the flavivirus DENV ( Verdonck et al, 2019), the filovirus EBOV (Verdonck et al, 2019), and the coronavirus SARS-CoV-2 (Karim et al, 2022) showed also activity against RSV, albeit with a low SI. A systematic SAR exploration of compound 1 focusing on Frontiers in Chemistry frontiersin.org structural variations at positions 1, 3 and 5 of the 7-aza-indole scaffold yielded various analogues with enhanced anti-RSV activity and no cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents

Martínez-Gualda

Graus²,

Camps³

et al. 2022

Front. Chem.

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RNA viral infections, including those caused by respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Venezuelan Equine encephalitis virus (VEEV), pose a major global health challenge. Here, we report the synthesis and screening of a series of pyrrolo[2,3-b]pyridines targeting RSV, SARS-CoV-2 and/or VEEV. From this campaign, a series of lead compounds was generated that demonstrated antiviral activity in the low single-digit micromolar range against the various viruses and did not show cytotoxicity. These findings highlight the potential of 3-alkynyl-5-aryl-7-aza-indoles as a promising chemotype for the development of broad-spectrum antiviral agents.

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“…In addition to erlotinib and sunitinib, 7-oxozeaenol which inhibits the activity of Numb-associated kinases also suppresses SARS-CoV-2 infection. Furthermore, Combination treatment with sunitinib and erlotinib exhibits a synergistic effect against SARS-CoV-2 infection [ 7 ]. In addition, inhibition of AAK1 by Jaktinib hydrochloride which is also a broad-spectrum JAK (Janus kinase) inhibitor is shown to slow the proliferation of SARS-CoV-2 [ 51 ].…”

Section: Numb-associated Kinases As Potential Broad-spectrum Antivira...mentioning

confidence: 99%

“…Silencing AAK1 , BIKE , GAK , and MPSK1 individually with siRNA is reported to suppress SARS-CoV2 infection in Calu-3 cells. Moreover, inhibitors of Numb-associated kinases such as sunitinib, erlotinib, and gefitinib are demonstrated to suppress SARS-CoV-2 infection [ 7 ]. So Numb-associated kinases are also proposed as possible therapeutic targets for broad-spectrum antiviral strategies.…”

Section: Introductionmentioning

confidence: 99%

Current thoughts on cellular functions of numb-associated kinases

Huang

Wang

2023

Mol Biol Rep

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Members of the Numb-associated kinase family of serine/threonine kinases play an essential role in many cellular processes, such as endocytosis, autophagy, dendrite morphogenesis, osteoblast differentiation, and the regulation of the Notch pathway. Numb-associated kinases have been relevant to diverse diseases, including neuropathic pain, Parkinson's disease, and prostate cancer. Therefore, they are considered potential therapeutic targets. In addition, it is reported that Numbassociated kinases have been involved in the life cycle of multiple viruses such as hepatitis C virus (HCV), Ebola virus (EBOV), and dengue virus (DENV). Recently, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten global health. Studies show that Numb-associated kinases are implicated in the infection of SARS-CoV-2 which can be suppressed by Numb-associated kinases inhibitors. Thus, Numb-associated kinases are proposed as potential host targets for broad-spectrum antiviral strategies. We will focus on the recent advances in Numb-associated kinases-related cellular functions and their potential as host targets for viral infections in this review. Questions that remained unknown on the cellular functions of Numb-associated kinases will also be discussed.

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Numb-associated kinases are required for SARS-CoV-2 infection and are cellular targets for antiviral strategies

Cited by 27 publications

References 59 publications

A new intracellular targeting motif in the cytoplasmic tail of the spike protein may act as a target to inhibit SARS-CoV-2 assembly

A new intracellular targeting motif in the cytoplasmic tail of the spike protein may act as a target to inhibit SARS-CoV-2 assembly

Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents

Current thoughts on cellular functions of numb-associated kinases

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