A potent therapy for the infectious coronavirus disease COVID-19 is urgently required with, at the time of writing, research in this area still ongoing. This study aims to evaluate the in vitro anti-viral activities of combinations of certain commercially available drugs that have recently formed part of COVID-19 therapy. Dual combinatory drugs, namely; Lopinavir-Ritonavir (LOPIRITO)-Clarithromycin (CLA), LOPIRITO-Azithromycin (AZI), LOPIRITO-Doxycycline (DOXY), Hydroxychloroquine (HCQ)-AZI, HCQ-DOXY, Favipiravir (FAVI)-AZI, HCQ-FAVI, and HCQ-LOPIRITO, were prepared. These drugs were mixed at specific ratios and evaluated for their safe use based on the cytotoxicity concentration (CC50) values of human umbilical cord mesenchymal stem cells. The anti-viral efficacy of these combinations in relation to Vero cells infected with SARS-CoV-2 virus isolated from a patient in Universitas Airlangga hospital, Surabaya, Indonesia and evaluated for IC50 24, 48, and 72 hours after viral inoculation was subsequently determined. Observation of the viral load in qRT-PCR was undertaken, the results of which indicated the absence of high levels of cytotoxicity in any samples and that dual combinatory drugs produced lower cytotoxicity than single drugs. In addition, these combinations demonstrated considerable effectiveness in reducing the copy number of the virus at 48 and 72 hours, while even at 24 hours, post-drug incubation resulted in low IC50 values. Most combination drugs reduced pro-inflammatory markers, i.e. IL-6 and TNF-α, while increasing the anti-inflammatory response of IL-10. According to these results, the descending order of effective dual combinatory drugs is one of LOPIRITO-AZI>LOPIRITO-DOXY>HCQ-AZI>HCQ-FAVI>LOPIRITO-CLA>HCQ-DOX. It can be suggested that dual combinatory drugs, e.g. LOPIRITO-AZI, can potentially be used in the treatment of COVID-19 infectious diseases.

Background. At the present time, COVID-19 vaccines are at the testing stage, and an effective treatment for COVID-19 incorporating appropriate safety measures remains the most significant obstacle to be overcome. A strategic countermeasure is, therefore, urgently required. Aim. This study aims to evaluate the efficacy and safety of a combination of lopinavir/ritonavir-azithromycin, lopinavir/ritonavir-doxycycline, and azithromycin-hydroxychloroquine used to treat patients with mild to moderate COVID-19 infections. Setting and Design. This study was conducted at four different clinical study sites in Indonesia. The subjects gave informed consent for their participation and were confirmed as being COVID-19-positive by means of an RT-PCR test. The present study constituted a randomized, double-blind, and multicenter clinical study of patients diagnosed with mild to moderate COVID-19 infection. Materials and Methods. Six treatment groups participated in this study: a Control group administered with a 500 mg dose of azithromycin; Group A which received a 200/50 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; Group B treated with a 200/50 mg dose of lopinavir/ritonavir and 200 mg of doxycycline; Group C administered with 200 mg of hydroxychloroquine and 500 mg of azithromycin; Group D which received a 400/100 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; and Group E treated with a 400/100 mg dose of lopinavir/ritonavir and 200 mg of doxycycline. Results. 754 subjects participated in this study: 694 patients (92.4%) who presented mild symptoms and 57 patients (7.6%) classified as suffering from a moderate case of COVID-19. On the third day after treatment, 91.7%–99.2% of the subjects in Groups A–E were confirmed negative by a PCR swab test compared to 26.9% in the Control group. Observation of all groups which experienced a significant decrease in virus load between day 1 and day 7 was undertaken. Other markers, such as CRP and IL-6, were significantly lower in all treatment groups ( p < 0.05 and p < 0.0001 ) than in the Control group. Furthermore, IL-10 and TNF-α levels were significantly elevated in all treatment groups ( p < 0.0001 ). The administration of azithromycin to the Control group increased CRP and IL-6 levels, while reduced IL-10 and TNF-α on day 7 ( p < 0.0001 ) compared with day 1. Decreases in ALT and AST levels were observed in all groups ( p < 0.0001 ). There was an increase in creatinine in the serum level of the Control, C, D, and E groups ( p < 0.05 ), whereas the BUN level was elevated in all groups ( p < 0.0001 ). Conclusions. The study findings suggest that the administration of lopinavir/ritonavir-doxycycline, lopinavir/ritonavir-azithromycin, and azithromycin-hydroxychloroquine as a dual drug combination produced a significantly rapid PCR conversion rate to negative in three-day treatment of mild to moderate COVID-19 cases. Further studies should involve observation of older patients with severe clinical symptoms in order to collate significant amounts of demographic data.

Peripheral nerve injury with gaps between 5 and 30 mm can result in permanent paralysis because axons are cut. The distance between axons, which is more than 1-2 cm, needs graft in the form of nerve connecting pipe in order to repair the defects. A synthesis of hollowfiber polyurethane-collagen coated by chitosan was carried out to identify its potential as treatment accelerator for peripheral nerve injury. The result of Fourier Transform Infrared (FTIR) analysis showed multiple links between chitosan and glutaraldehyde, which can be seen in wavenumber shift from 1080-1100 cm-1 to 1002 cm-1. The degradation test result revealed that the sample displayed mass loss after it was soaked in simulated body fluid(SBF) for seven days. Polyurethanecan be degraded in the body after 30 days. This converges with the nerve mechanism that regenerates at the rate of 1 mm/day or 1 inch/month. The result of tensile test indicated that modulus values of chitosan coating variation of 1%, 1.5%, and 2% were 4.75 MPa, 4.74 MPa, and 7.67 Mpa respectively. The outcome of scanning electron microscope(SEM)showed that hollow fiberhas a diameter of 2.021-2.032 mm, which matches the diameter of peripheral nerves ranging from 1.5 to 3 mm and the membrane pore size of 31.33-39.65 μm. The result of MTT assay demonstrated that the percentage of viable fibroblastBHK-21cells was exceeding 50%, which means that the sample does not have toxic properties. The result of this study is expected to provide theoretical basis for the utilization of polyurethane-collagen coating chitosan as nervegraft for theraphy of peripheral nerve injury. The utilization is possible due to the fact that the composite exhibits biocompatible, regenerative, and easily degradable characteristics. Moreover, it could become an alternative solution to answer the need of a more affordable and easier-to-produce nerve graft, so it can be mass-produced in Indonesia.

Background: The prevalence of COVID-19 cases in Indonesia until June 9th 2020, Government has confirmed the number of 32.076 positive cases from 34 provinces in Indonesia with 1.923 fatalities. Along with the development of technology, stem cell-based biological medical therapy, and stem cell-based immunotherapy were developed to find out its potential in the case of COVID-19 treatment besides using chemical drugs as a therapy.Methods: In this study, in vitro research will be conducted to determine the potential of hematopoietic stem cells (HSC) against SARS-CoV-2 (COVID-19) viruses with virus isolates from Indonesia. The SARS-CoV-2 virus was planted in rat kidney cells and Vero cells, then cells that had been planted with the virus were given HSC cells and then evaluated at 24, 48, and 72 hours. The evaluation is done by collecting cells and supernatant from the cell plate and then evaluating the viral load using a Polymerase Chain Reaction (PCR) machine.Results: The results showed that the addition of HSC on cells that had been infected by SARS-CoV-2 decrease in viral load within 24 to 72 hours in all variations of Multiples of Infection (MoI) values.Conclusions: The administration of HSC cells has the potential to eliminate SARS-CoV-2 virus. Although this research is an in vitro study, this study could be the basis for the development of alternative stem cell-based therapies to handle COVID-19 cases in Indonesia.

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