EZRIN PEPTIDE 1 FOR USE IN A METHOD OF TREATING COVID-19

Abstract

The present invention relates to Ezrin peptide 1 and/or an analogue thereof for use in a method of treating COVID-19 and for use in a method of treating post COVID-19 syndrome.

Claims

1. A method of treating COVID-19 or post COVID-19 syndrome in a subject, comprising administering to the subject Ezrin peptide 1, wherein the Ezrin peptide 1 comprises the amino acid sequence NH2_Thr-Glu-Lys-Lys-Arg-Arg-Glu-Thr-Val-Glu-Arg-Glu-Lys-Glu_COOH (SEQ ID NO:1).

2. (canceled)

3. The method of claim 1, wherein the Ezrin peptide 1 is dissolved in saline solution for subcutaneous administration.

4. The method of claim 1, wherein the Ezrin peptide 1 is formulated for oral administration.

5. The method of claim 1, wherein the Ezrin peptide 1 is formulated for inhalation or for intranasal administration.

6. The method of claim 1, wherein the Ezrin peptide 1 is administered daily.

7. The method of claim 1, wherein the subject is a human tested positive for SARS-COV-2 or suspected of being infected with SARS-COV-2.

8. The method of claim 1, wherein the Ezrin peptide 1 is administered in a pharmaceutical composition comprising Ezrin peptide 1 and a pharmaceutically acceptable carrier.

9. The method of claim 8, wherein the composition is formulated either for subcutaneous administration, oral administration, inhalation or intranasal administration.

10. A method of treating COVID-19 or post COVID-19 syndrome in a subject, comprising administering to the subject an analogue of Ezrin peptide 1 of the formula (I) TABLE-US-00002 (I) (SEQIDNO:5) NH2X1-Glu-Lys-Lys-Arg-Arg-Glu-Thr-Val-Glu-Arg-Glu- X2-X3COOH where X1, X2 and X3 are identical or different and are non-polar amino acid residues.

11. The method of claim 10, wherein X1, X2 and X3 are identical and glycine residues.

12. The method of claim 10, wherein the analogue is dissolved in saline solution for subcutaneous administration.

13. The method of claim 10, wherein the analogue is formulated for oral administration.

14. The method of claim 10, wherein the analogue is formulated for inhalation or intranasal administration.

15. The method of claim 10, wherein the analogue is administered daily.

16. The method of claim 10, wherein the subject is a human tested positive for SARS-COV-2 or suspected of being infected with SARS-COV-2.

17. The method of claim 10, wherein analogue of Ezrin peptide 1 is used in combination with Ezrin peptide 1.

18. The method of claim 10, wherein the analogue of Ezrin peptide 1 is administered in a pharmaceutical composition comprising an analogue of Ezrin peptide 1, or a combination thereof with Ezrin peptide 1, and a pharmaceutically acceptable carrier for use in a method of treating COVID-19 or post COVID-19 syndrome.

19. The method of claim 10, where the amino acids are selected from the group consisting of glycine, alanine, valine, leucine, methionine, isoleucine, proline, phenylalanine, tryptophan and combinations thereof.

Description

EXAMPLES

Example 1: 69 Year Old Patient

[0045] risk factors: adipositas, AV block 1.sup.st grade, hypertonus [0046] Skiing trip to Switzerland (Grindelwald) from March 1.sup.st-7.sup.th [0047] Course of Disease: [0048] 08.03.2020: Loss of taste [0049] 09.03.2020: Feeling ill with fatigue and headache [0050] 11.03.2020: Same symptoms but fever over 38? C. [0051] 12.03.2020: Coronavirus testing; Same symptoms with fever to 39? C., [0052] 13.03.2020: Positive test result; persisting symptoms with starting dry cough [0053] 14.03.2020: 1.sup.st Ezrin peptide 1 administration in the evening, persisting symptoms [0054] 15.03.2020: 2.sup.nd Ezrin peptide 1 administration in the morning, increasing symptoms [0055] 16.03.2020: 3.sup.rd Ezrin peptide 1 administration in the morning, increasing symptoms with strong eye pain [0056] 17.03.2020: 4.sup.th Ezrin peptide 1 administration in the morning, increasing symptoms with more cough [0057] 18.03.2020: 5.sup.th Ezrin peptide 1 administration in the morning, significant signs of recovery, no eye pain, decreasing fever [0058] 19.03.2020: 6.sup.th Ezrin peptide 1 administration in the morning, significant signs of recovery, normal body temperature, no fatigue [0059] 20.03.2020: 7.sup.th Ezrin peptide 1 administration in the morning, return of taste, good general condition [0060] 21.03.2020: 8.sup.th Ezrin peptide 1 administration in the morning, no signs of illness anymore [0061] Dosage: 2 mg Ezrin peptide 1, dissolved in saline solution, separated into 10 single doses (? 0.2 mg), [0062] 1 single dose per subcutaneous administration daily

[0063] Surprisingly, the severity of symptoms after administration was significantly lower than one would have expected in a patient of this risk group. The course of the disease was also significantly shorter compared to the course of the disease expected for patients of this risk group. Severe complications such as fibrosis of the lungs did not occur.

Example 2: 64 Year Old Male Patient

[0064] Risk factors: hypertonus, asthma, COPD, hyperchlosterinaemia [0065] Permanent medication: [0066] Candesartan 8 mg [0067] Foster (beclometason dipropionate, formoterol fumarate dihydrate) [0068] Simvastatin [0069] Dosage: Six single doses ? 2 mg Ezrin peptide 1, dissolved in saline solution and administered subcutaneously (s.c.). [0070] Course of Disease: [0071] 23.04.2020: First occurrence of fever, 38.4? C.; [0072] 24.04.2020: Severe clinical symptoms with high fever above 39.0? C., nausea, loss of taste, respiratory distress, dry cough, severe headache; Corona-PCR was prepared with positive result for SARS-COV-2, First Ezrin peptide 1, 2 mg subcutaneous (s.c.) in the evening; [0073] 25.04.2020: In the morning second dose of Ezrin peptide 1, 2 mg s.c.; body temperature dropped to 37.5? C. in the morning, still general weakness, shortness of breath, cough, loss of appetite, in the evening body temperature again 39.0? C.; [0074] 26.04.2020: Third administration of Ezrin peptide 1, 2 mg s.c.; Still loss of appetite, slight cough, in the evening body temperature still 37.5? C.; [0075] 27.04.2020: Fourth dose of Ezrin peptide 1, 2 mg s.c.; Slight cough, slight headache, body temperature 37.4? C.; [0076] 28.04.2020: Fifth administration of Ezrin peptide 1, 2 mg s.c.; Only slight pain of touching the scalp, still slight weakness, body temperature 37.3? C.; [0077] 30.04.2020: Sixth administration of Ezrin peptide 1, 2 mg s.c.; Significant improvement of clinical symptoms, normal temperature, macrohaematuria (inconspicuous urological consultation), CRP level >100 mg/l, a CT of the thorax was carried out because of suspected pneumonia; [0078] 01. to 04.05.2020: antibiotic coverage due to increased CRP level, taste completely returned, no more cough, no more fever, clinical well-being.

Example 3: 79 Year Old Male Patient

[0079] Risk factor/pre-existing illnesses: COPD, Diabetes mellitus Typ2, 2 artificial heart valves, Apoplexia in 2018 [0080] Dosage: Single doses of 2 mg Ezrin peptide 1, dissolved in saline solution and administered subcutaneously (s.c.) on Dec. 23, 2020 followed by 0.2 mg/d Ezrin peptide 1 (single doses, s.c.) for four days. [0081] Course of Disease: [0082] First symptoms: Beginning of December 2020: Cough, loss of sense of smell and taste; [0083] Continuously worsening of cough, fatigue and loss of appetite, shortness of breath since 18.12.2020; [0084] Positive Antigen-Test (Lateral-flow-test) 22.12.2020, positive PCR test for SARS-Cov2 on 23.12.2020; [0085] 23.12.2020 begin of HEP-1 therapy with 2 mg/d for two days followed by 0.2 mg/d for four (4) days; [0086] 25.12.2020 significant improvement of cough and general condition; [0087] No further symptoms after completion of HEP-1 therapy.

Example 4: 49 Year Old Female Patient

[0088] Risk factor/pre-existing illnesses: Hypertension [0089] Dosage: Single doses of 2 mg/d Ezrin peptide 1, dissolved in saline solution and administered subcutaneously (s.c.) for 2 days, followed by 0.2 mg/d Ezrin peptide 1 (single doses, s.c.) for four (4) days. [0090] Course of Disease: [0091] First symptoms: 19.12.2020 Severe cough, fatigue, chills; [0092] Further symptoms: 21.12.2020 diarrhoea, thoracic pain, angina pectoris, shortness of breath; [0093] Positive Antigen-Test (Lateral-flow-test) 21.12.2020, positive PCR test for SARS-Cov2 on 23.12.2020; [0094] 23.12.2020 begin of HEP-1 therapy with 2 mg/d for two days followed by 0.2 mg/d for four days; [0095] 25.12.2020 significant improvement of cough and general condition; [0096] No further symptoms after completion of HEP-1 therapy.

Example 5: 53 Year Old Male Patient

[0097] Risk factor/pre-existing illnesses: Hypertension [0098] Initial dosage: Single doses of 2 mg/d Ezrin peptide 1, dissolved in saline solution and administered subcutaneously (s.c.) for 2 days, followed by 0.2 mg/d Ezrin peptide 1 (single doses, s.c.) for four days. [0099] Subsequent dosage: 0.2 mg/d Ezrin peptide 1 (single doses, s.c.) for fourteen (14) days. [0100] Course of Disease: [0101] First symptoms: 23.12.2020 Severe cough and rhinitis, limb pains, sore throat, loss of sense of smell and taste, angina pectoris, fatigue, chills; [0102] 23.12.2020 begin of HEP-1 therapy with 2 mg/d (single dose) for two days followed by 0.2 mg/d for four days; [0103] 26.12.2020 significant improvement of symptoms; [0104] 28.12.2020: PCR-Re test for SARS-Cov2 still positive; [0105] No further symptoms after completion of HEP-1 therapy until 13.01.2021, then severe shortness of breath; [0106] 15.01.2021: Administration of 0.2 mg/d Ezrin peptide 1 (single dose) for fourteen (14) days; [0107] No further shortness of breath after completion of HEP-1 therapy.

Example 6: 68 Year Old Female Patient

[0108] Risk factor/pre-existing illnesses: unknown [0109] Dosage: Single doses of 0.2 mg/d Ezrin peptide 1, dissolved in saline solution and administered subcutaneously (s.c.) for ten (10) days. [0110] Course of Disease: [0111] First symptoms: 09.12.2020 fever, cough, headache, shortness of breath and fatigue; [0112] Positive PCR test for SARS-Cov2 on 10.12.2020; [0113] 10.12.2020 begin of HEP-1 therapy with 0.2 mg/d for ten (10) days; [0114] 14.12.2020 significant improvement of symptoms; [0115] 20.12.2020 complete recovery of symptoms.