Surveillance at the level of the virus, humans, and geographical origins and distributions is a critical step in combating Covid-19. While molecular surveillance involves large-scale sequencing of viral genomes, digital surveillance utilizes big data at the population level.
• CSIR has undertaken community-level screening at Kolar, Karnataka where CSIR-IGIB is leading the team in setting up a model for community surveillance. This is being done in collaboration with NIMHANS, THSTI (DBT), and TATA Sons. Around 1000 random samples that included 200 healthcare workers from a database of 1 million people were screened by a mix of RT-PCR assays and Rapid Antibody test and proper ELISA. This model was run successfully and can be replicated in different cities pan India.
• CSIR has also undertaken genome sequencing with samples from different geographical regions of the country. The computational support is being provided by IIIT, Hyderabad, and INTEL.
• Sequencing the viral genomes in India is the need of the hour to understand the virus dynamics such as its spread and mutation frequency and the impact on the severity of the disease and implications for the vaccine, drug and diagnostic development. From India, about 200 sequences have been reported as on date, of which 104 sequences have been submitted by CSIR-IGIB in collaboration with National Centre for Disease Control. Additionally, CSIR-CCMB has sequenced 50 new viral genomes. Thus 174 genomes have been sequenced so far at CSIR.
Testing COVID-19 Samples
The key to flattening the curve of growth in Coronavirus cases is the detection of the infected at the earliest and isolating them. Rapid diagnosis, therefore, is the need of the hour towards which CSIR has made major contributions using multiple strategies.
During the week 7-14 May CSIR labs across the nation have tested 3023 samples for COVID-19. So far, in total, CSIR labs have tested >10,000 samples.
No. of tests
CSIR-CFTRI and CSIR-CLRI have also contributed to 8544 in Mysuru and 5000 tests in Chennai respectively so far by providing the State Government with RT-PCR machines.
6 Research Scholars from CSIR-CLRI have also supported the King College of Preventive Medicine in testing 1300 samples over the last week.
Faster and Cheaper Diagnostics
CSIR-CCMB has been pooling samples that belong to areas with lower than 2% COVID-19 prevalence rates for diagnostics using RT-PCR. The SOP for this strategy is now publicly available.
It has now developed a new strategy to pool samples from all different districts of a state and test them together. Every single sample is barcoded using PCR at the sample collection centre. These samples will be sent to a central point like CSIR-CCMB which has Next-Gen Sequencing facilities, which can test up to 50,000 samples in two days.
The centre will now test its pilot run, with support from SynGene, Bengaluru. If successful, the plan would be extended to the states of Telangana and Karnataka. This strategy aims to do faster testing of a large population, at about 0.3$ (~Rs 25) per sample.
Drugs & Vaccines against COVID-19
As the research into SARS-CoV-2 is in its early days and our understanding is evolving each day, it is critical to deploy all possible strategies to combat the virus. CSIR’s strategy has involved repurposing existing drugs against COVID-19, discovering new drugs and exploring natural products and phtypharmaceuticals for developing drugs. CSIR has achieved considerable success in this endeavour working with major pharma companies. Some recent developments are outlined here.
• Clinical trials: CSIR has received approval from the Drug Controller General of India (DGCI) for two clinical trial drugs – a phytopharmaceutical and Favipiravir – to treat COVID-19. The trial will begin within a week.
• Sepsivac against COVID-19 with Cadila: CSIR and Cadila Pharmaceuticals have received regulatory approval for initiating clinical trials to evaluate the efficacy of an existing gram-negative sepsis drug called Sepsivac for COVID-19 patients. The clinical trials are being carried out among critically ill patients at PGI Chandigarh, AIIMS New Delhi and AIIMS Bhopal). Clinical trial will also be carried out among subjects at risk of getting infected (4000 participants) and positive patients, hospitalized but not critically ill (480 participants).
• Phytopharmaceutical ACQH with Sun Pharma: ACQH has been developed by CSIR-IIIM and DBT-ICGEB and is active against all four subtypes of dengue virus. It is being repositioned for treating COVID-19. It has earlier completed human safety phase 1 trial and now approval has been granted for Phase II trials on COVID-19 patients.
• Favipiravir with Cipla: Favipiravir is a drug used for the treatment of influenza. It is a safe drug and its trial can be expected to be completed in about 1.5 months. If tests are successful, the drug could be available soon (as its patent has expired) at an affordable price. The synthetic process has been developed at CSIR-IICT, which has provided API and key starting materials to Cipla. Cipla has received approval for phase II clinical trials, which will begin soon.
• Remdesivir: CSIR-IICT has developed API and KSM and shared the process of technology with industries. The API of Remdesivir is being provided by CSIR-IICT to CIPLA, which is one of the licensees that has received a voluntary license from Gilead.
• Clinical trials with ICMR and Ministry of Ayush: CSIR is collaborating with studies on Ayurveda interventions as prophylaxis and as an add-on to standard care to COVID-19. Ayurvedic medicines such as Ashwagandha, Yashtimadhu, Guduchi Pippali, and a polyherbal formulation (Ayush-64) will be tested on health workers and those working in COVID-19 high-risk areas.
• In-silico screening of existing drugs and natural products: Virtual screening of about 7100 molecules is being carried out including FDA approved anti-virals, molecules from anti-tussive ayurvedic formulations, and phytochemicals by docking against the Main protease (Mpro) and RNA dependent RNA polymerase (RdRp), and Human ACE2, the key targets of SARS-CoV-2. Extensive docking studies have been carried out by CSIR-CLRI and CSIR-NEIST on Saquinavir, Sirolimus and Erythomycine, Zafirlinkast, Indinavir, Zanavir, Cefdivir, Tetracyclin, Darunavir, etc. CSIR-NEIST has obtained data on the interaction of 7 antivirals with 3 CL-Pro including Paritaprevir, Simaprevir, etc. Docking studies of 750 analogues of derivatives of Hydroxychloroquine and chloroquine were initiated by CSIR-IITR which suggested two derivatives with spike protein as a target.
• SARS-CoV-2 viral assays: To provide impetus to the drug discovery and vaccine testing in the country CSIR-CCMB has set up the SARS-CoV-2 viral culture systems. It has entered into a collaboration with Eyestem Research Private Limited. The research team will use the human lung epithelial cell culture system provided by Eyestem as part of its anti-covid screening (ACS) platform.
• Antibodies and serology approach: CSIR through its NMITLI programme has approved a project for the development of human monoclonal antibodies (hmAbs) that can neutralize SARS-CoV-2 in patients. The project would be implemented by a multi-institutional and multi-disciplinary team comprising NCCS, IIT-Indore, PredOmix Technologies and Bharat Biotech International. The project aims to generate hmAbs to SARS-CoV-2 from the convalescent phase of COVID-19 patients and select high affinity and neutralizing antibodies. The project also aims to anticipate future adaptation of the virus and generate hmAbs clones that can neutralize the mutated virus and could be readily available for combating future SARS-CoV infections.
CSIR-CCMB has also entered into an MoU with the University of Hyderabad and Vins Bioproducts Ltd. to enable the development of antisera against SARS-CoV-2 using the inactivated virus in horses, which is amenable for large-scale production. Antisera is the blood serum containing antibodies which can be used for passive immunity.
Hospital Assistive Devices & PPEs
Ever since the pandemic struck, CSIR has been introducing low-cost and effective hospital assistive devices and PPEs and consistently improving their efficiency and design. Many of them have been transferred to the industry while some are at the stage of beta testing, which will be followed by certification.
Bi-Level Positive Airway Pressure System by CSIR-NAL: The highlight of the week and one that garnered considerable attention and positive responses was the development of the BiPAP Ventilator by the CSIR-National Aerospace Laboratories. The ventilator is a microcontroller-based system with a HEPA filter (Highly Efficient Particulate Air Filter). These unique features help to alleviate the fear of the virus spread.
It is simple to use without any specialized nursing, cost-effective, compact and configured with the majority of indigenous components. It has features like Spontaneous, CPAP, Timed, AUTO BIPAP modes with provision to connect Oxygen concentrator or Enrichment unit externally.
The ventilator is ideal for treating COVID-19 patients in wards, make shift hospitals, dispensaries and home. It has been certified for safety and performance by NABL accredited agencies. The system has undergone stringent biomedical tests and beta clinical trials at NAL Health Centre. The entire process has been done in a record 36 days, competing with global standards for speed.
NDA has been signed with 6 MSMEs for commercialization of the technology – Cyient Technologies, Bengaluru; Datasol, Bengaluru; Apollo Computing, Hyderabad; Paras Defence, Mumbai; Redimo, Bangalore; and Kavitual, Gujarat.
Protective Coverall: CSIR-NAL Bengaluru developed a coverall protective suit for the protection of healthcare workers attending to COVID-19 patients. The polypropylene spun laminated multi-layered non-woven fabric has been developed in collaboration with MAF Clothing and has undergone stringent testing. The production capacity of the coverall, initially pegged at 30,000 has now been enhanced to 50,000 units per day.
Respiratory Assistance Intervention Device by CSIR-CSIO: Functional testing of the developed prototype as per targeted specifications has been completed using a Ventilator calibrator and artificial test lung. Initial two rounds of validation have been completed in discussions with anaesthesiologist of GMCH, Chandigarh and the final round of validation in progress. Expected to be completed by May 16, 2020. ToT under process in discussions with M/s. Forbes (India), Mumbai, and M/s. LM Healthcare, Panchkula.
Oxygen Enrichment Unit by CSIR-NCL: OEU is one of the critical needs of COVID- 19 patients is the need to meet the oxygen requirements due to their lungs being compromised. Oxygen enrichment unit (OEU) to increase the oxygen concentration from the ambient air of 21-22% to 38-40% has been developed by CSIR-NCL and Genrich Membranes, a start-up innovation venture. It produces enriched oxygen for patients in the home and hospital settings allowing enhancement of oxygen levels up-to 40%. It has passed all 11 tests at TUV Reinlands and is undergoing clinical trials.
HCARD — Robotic Device for Frontline Healthcare Warriors: CSIR-CMERI (Central Mechanical Engineering Research Institute), Durgapur has developed a “Hospital Care Assistive Robotic Device” to safeguard healthcare workers by reducing their exposure to infected patients.
The robotic device possesses various features including navigation, drawer activation for providing medicines and food to patients, sample collection and audio-visual communication and can be controlled and monitored by a nursing booth with a control station. The robot works with both automatic as well as manual modes of navigation.
Face Shield by CSIR-CECRI: CSIR-CECRI has developed a 3-D printed face shield that has been certified by CIPET. The Institute has partnered with a company 3D Lycan, Bangalore which can make 500 pieces/day (3D printed) and bulk orders can go up to 30,000/day based on the injection mold process.
Face Mask from CSIR-CMERI: The face masks developed by CSIR-CMERI have received certification from SITRA and scale-up is being explored with mechanization and MSMEs.
Supply Chain & Logistics
The success of development, deployment and operationalisation depends on the entire supply chain being in place and functional, especially in the current lockdown scenario in the country and worldwide. CSIR labs are geared up to facilitate regional demands for materials and supplies for testing labs, PPEs, medical supplies, etc. The database of potential suppliers of quality products is under preparation. This platform will also showcase and make available the different CSIR products developed for the management of the COVID-19 pandemic.
• AarogyaPath: Following the successful launch of the Kisan Sabha App recently, steps have been initiated to develop Aarogyapath, a National Healthcare Supply Chain Management System to address COVID-19 and similar pandemics. This platform will act as a single stop solution for all national healthcare needs. The domain http://aarogyapath.in/ has been registered. A knowhow management agreement entitled “Development of web application AarogyaPath: National Healthcare Supply Chain Management System” between CSIR and private partner Sarvodaya Infotech Private Limited was signed on 13 May 2020.