Disease Information

General Information of the Disease (ID: DIS00143)

• Name: COVID-19
• ICD: ICD-11: 1D92

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 5 drug(s) in total

6-N-ethyl-netilmicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Signal transducer activator transcription 3 (STAT3) [1]

• Sensitive Disease: Corona Virus Disease 2019 [ICD-11: 1D92.0]
• Sensitive Drug: 6-N-ethyl-netilmicin
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Immune cells; Blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Flow cytometry
• Mechanism Description: Baricitinib is a selective Janus kinase (JAK)1/JAK2 inhibitor with a known anti-inflammatory profile in patients with autoimmune diseases.Baricitinib was also shown to reduce multiple cytokines and biomarkers implicated in COVID-19 pathophysiology.

MPA

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Interleukin-1 beta (IL1B) [2]

• Sensitive Disease: Corona Virus Disease 2019 [ICD-11: 1D92.0]
• Sensitive Drug: MPA
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: SARS coronaviruses have been shown to trigger the inflammasome and the release of interleukin-1beta (IL-1beta).Canakinumab is an IL-1beta antibody that neutralises the activity of IL-1beta.

Remdesivir

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Non-structural protein 12 (NSP12) [3]

• Resistant Disease: Corona Virus Disease 2019 [ICD-11: 1D92.0]
• Resistant Drug: Remdesivir
• Molecule Alteration: Single mutations; E802A+E802D+V791I+C799F
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Huh-7.5 cells; N.A.; Homo sapiens (Human); CVCL_7927
• Experiment for Molecule Alteration: Biochemical assay
• Experiment for Drug Resistance: In-vitro infection assay
• Mechanism Description: Remdesivir target nsp12, thereby reducing the viral load. However, the emergence of resistant mutations in 3CLpro and nsp12 could impact the efficiency of these small molecule drug therapeutics.

Sotrovimab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Moesin (MSN) [4]

• Resistant Disease: Corona Virus Disease 2019 [ICD-11: 1D92.0]
• Resistant Drug: Sotrovimab
• Molecule Alteration: Mutations; E484K+F490S+S494P
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: Vero E6 cells; Kideny; Homo sapiens (Human); N.A.
• In Vitro Model: BHKG43 cells; Kideny; Homo sapiens (Human); N.A.
• In Vitro Model: HEK 293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: qRT-PCR; Deep sequencing assay
• Experiment for Drug Resistance: Immunofluorescence assay
• Mechanism Description: Monoclonal antibodies targeting the Spike protein of SARS-CoV-2 are effective against COVID-19 and might mitigate future pandemics. However, their efficacy is challenged by the emergence of antibody-resistant virus variants.

Bamlanivimab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Moesin (MSN) [4]

• Resistant Disease: Corona Virus Disease 2019 [ICD-11: 1D92.0]
• Resistant Drug: Bamlanivimab
• Molecule Alteration: Mutations; E340K
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: Vero E6 cells; Kideny; Homo sapiens (Human); N.A.
• In Vitro Model: BHKG43 cells; Kideny; Homo sapiens (Human); N.A.
• In Vitro Model: HEK 293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: qRT-PCR; Deep sequencing assay
• Experiment for Drug Resistance: Immunofluorescence assay
• Mechanism Description: Monoclonal antibodies targeting the Spike protein of SARS-CoV-2 are effective against COVID-19 and might mitigate future pandemics. However, their efficacy is challenged by the emergence of antibody-resistant virus variants.

Clinical Trial Drug(s) 1 drug(s) in total

Pristinamycin I

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Interleukin-1alpha (IL1A) [5]

• Sensitive Disease: Corona Virus Disease 2019 [ICD-11: 1D92.0]
• Sensitive Drug: Pristinamycin I
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Anakinra, a recombinant IL-1 receptor antagonist, might help to neutralise the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hyperinflammatory state, which is considered to be one cause of acute respiratory distress among patients with COVID-19.

Key Molecule: Interleukin-1 beta (IL1B) [5]

• Sensitive Disease: Corona Virus Disease 2019 [ICD-11: 1D92.0]
• Sensitive Drug: Pristinamycin I
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Anakinra, a recombinant IL-1 receptor antagonist, might help to neutralise the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hyperinflammatory state, which is considered to be one cause of acute respiratory distress among patients with COVID-19.

Investigative Drug(s) 1 drug(s) in total

Tixagevimab/Cilgavimab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Moesin (MSN) [4]

• Resistant Disease: Corona Virus Disease 2019 [ICD-11: 1D92.0]
• Resistant Drug: Tixagevimab/Cilgavimab
• Molecule Alteration: Mutations; L100I + K103N + P225H
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Vero E6 cells; Kideny; Homo sapiens (Human); N.A.
• In Vitro Model: BHKG43 cells; Kideny; Homo sapiens (Human); N.A.
• In Vitro Model: HEK 293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: qRT-PCR; Deep sequencing assay
• Experiment for Drug Resistance: Immunofluorescence assay
• Mechanism Description: Monoclonal antibodies targeting the Spike protein of SARS-CoV-2 are effective against COVID-19 and might mitigate future pandemics. However, their efficacy is challenged by the emergence of antibody-resistant virus variants.

Key Molecule: Moesin (MSN) [4]

• Resistant Disease: Corona Virus Disease 2019 [ICD-11: 1D92.0]
• Resistant Drug: Tixagevimab/Cilgavimab
• Molecule Alteration: Mutations; L2003M
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• Experiment for Molecule Alteration: qRT-PCR; Deep sequencing assay
• Experiment for Drug Resistance: Immunofluorescence assay
• Mechanism Description: Monoclonal antibodies targeting the Spike protein of SARS-CoV-2 are effective against COVID-19 and might mitigate future pandemics. However, their efficacy is challenged by the emergence of antibody-resistant virus variants.

References

• Ref 1: Baricitinib restrains the immune dysregulation in patients with severe COVID-19 J Clin Invest. 2020 Dec 1;130(12):6409-6416. doi: 10.1172/JCI141772.
• Ref 2: Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study Int J Infect Dis. 2021 Mar;104:433-440. doi: 10.1016/j.ijid.2020.12.073. Epub 2020 Dec 29.
• Ref 3: SARS-CoV-2 Resistance to Small Molecule Inhibitors. Curr Clin Microbiol Rep. 2024 Sep;11(3):127-139.
• Ref 4: Identification of antibody-resistant SARS-CoV-2 mutants via N4-Hydroxycytidine mutagenesis. Antiviral Res. 2024 Nov;231:106006.
• Ref 5: Anakinra for severe forms of COVID-19: a cohort study Lancet Rheumatol. 2020 Jul;2(7):e393-e400. doi: 10.1016/S2665-9913(20)30164-8. Epub 2020 May 29.